George Makavos

Arterial stiffness and coronary artery disease.

Purpose of review The current traditional risk scores are not sufficient to predict the full incidence of cardiovascular disease. In this brief review, we discuss the pathophysiological mechanisms through which arterial stiffness affects cardiac function and the additive value of markers of arterial stiffness, to detect the presence of coronary artery disease (CAD) and predict adverse outcome in these patients. Recent findings Arterial stiffness causes early arrival of wave reflections in systole instead of diastole and, thus, increases systolic afterload and reduces diastolic coronary perfusion pressure. Abnormal collagen turnover, cytokines, and metalloproteinase activity are common biochemical links between vascular and myocardial stiffness. Pulse wave velocity, augmentation index, and central pressures measured by simple noninvasive methods are related to atheromatic plaque vulnerability, incidence, severity, and extent of CAD. Recent meta-analyses have shown the additive value of markers of arterial stiffness, and particularly of pulse wave velocity, to detect CAD, predict cardiovascular events, and reclassify patients to a higher cardiovascular risk. Studies assessing whether reduction of arterial stiffness is associated with improved prognosis are lacking. Summary Markers of arterial stiffness are useful tools to identify early atherosclerosis and adverse clinical outcomes in young adults and individuals with a modest risk factor profile. Assessing arterial stiffness may facilitate cardiovascular risk stratification beyond traditional risk scores.

Multidimensional contractile reserve predicts adverse outcome in patients with severe systolic heart failure: a 4-year follow-up study

Left ventricular contractile reserve is a prognostic indicator for adverse outcome in patients with severe chronic heart failure with reduced ejection fraction (HFrEF). We investigated the dobutamine‐induced changes of LV multidimensional deformation and their predictive value for cardiac mortality of patients with severe chronic HFrEF.

Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in PsoriasisCLINICAL PERSPECTIVE

Background— Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis. Methods and Results— One hundred fifty psoriasis patients were randomized to receive an anti–IL-12/23 (ustekinumab, n=50), anti–tumor necrosis factor-a (TNF-&agr;; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-&agr;, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: −17.7% versus −19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-&agr;, and IL-6 post-treatment (P<0.05). Compared with anti–TNF-&agr; and cyclosporine, anti–IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (−25% versus −4% versus −2%), malondialdehyde (−27% versus +5% versus +26%), and NT-proBNP(−26% versus −13.6% versus 9.1%) and increase of fetuin-a (P<0.01). Pulse wave velocity and augmentation index were improved only after anti–IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting–untwisting (P<0.05). Conclusions— In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-&agr; inhibition or cyclosporine treatment. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857.

Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives

We investigated the association of endothelial glycocalyx damage with arterial stiffness, impairment of coronary microcirculatory function, and LV myocardial deformation in 320 untreated hypertensives and 160 controls. We measured perfused boundary region (PBR) of the sublingual microvessels, a marker inversely related with glycocalyx thickness, coronary flow reserve (CFR), and Global Longitudinal strain (GLS) by echocardiography, pulse wave velocity (PWV), and central systolic blood pressure (cSBP). Hypertensives had higher PBR, PWV cSBP, and lower CFR and GLS than controls (P < .05). In hypertensives, increased PBR was associated with increased cSBP, PWV, and decreased CFR and GLS after adjustment for age, sex, BMI, smoking LV mass, heart rate, hyperlipidemia, and office SBP (P < .05). PBR had an additive value to PWV, CFR, and office SBP for the prediction of abnormal GLS (x2 = 2.4‐3.8, P for change = .03). Endothelial glycocalyx is impaired in untreated hypertensives and is related to arterial stiffness, coronary, and myocardial dysfunction.

Deformation Analysis of Myocardial Layers Detects Early Cardiac Dysfunction after Chemotherapy in Bone Marrow Transplantation Patients: A Continuous and Additive Cardiotoxicity Process

Background Chemotherapy‐induced cardiotoxicity has not been extensively validated in bone marrow transplantation (BMT) patients. Speckle‐tracking echocardiography is a sensitive method for the detection of subclinical cardiac dysfunction. Methods Cardiac function was prospectively assessed in 80 patients (44 men; mean age, 45 ± 11 years) after BMT for non‐Hodgkins lymphoma and acute or chronic myeloid leukemia by means of various echocardiographic techniques. Before chemotherapy for BMT, 89% of the patients had previously been treated with anthracyclines. Patients had normal left ventricular ejection fraction (LVEF). Left ventricular (LV) global longitudinal strain (GLS), subendocardial and subepicardial longitudinal strain, circumferential strain, LV twist, and right ventricular GLS were measured by speckle‐tracking, and (2) three‐dimensionally derived LVEF and right ventricular ejection fraction were also assessed. Abnormal LVEF was defined as <53%. Studies were performed before (baseline) and 1, 3, 6, and 12 months after chemotherapy conditioning followed by BMT. Results Impaired LV GLS values were observed at 1 month after chemotherapy and at 3, 6, and 12 months compared with baseline (−20 ± 2.2% at baseline, −18.4 ± 2.1% at 1 month, −17.3 ± 2.2% at 3 months, −17.1 ± 2.1% at 6 months, and −17.1 ± 2.2% at 12 months; P = .001). Early LV GLS changes were driven mostly by changes in subendocardial longitudinal strain (−22.5 ± 2.4% at baseline, −20.5 ± 2.3% at 1 month, −19.2 ± 2.3% at 3 months, −19.2 ± 2.4% at 6 months, and −19.1 ± 2.4 at 12 months; P = .001), whereas significant subepicardial strain changes were observed at 3 months after BMT. Compared with baseline, right ventricular GLS was also impaired early after chemotherapy. Compared with baseline, LVEF was slightly reduced (P = .02) at the end of the follow‐up. Among echocardiographic markers, LV GLS at 1 month had the strongest predictive value for abnormal LVEF (<53%) at 12 months (area under the curve 0.86; 95% CI, 0.76–0.96). A cutoff LV GLS value of −18.4% had sensitivity of 84.6% and specificity of 71.9% for the identification of abnormal LVEF at the end of follow‐up. Conclusions In BMT patients, myocardial deformation analysis detected early and progressive subclinical cardiac dysfunction. Impaired LV GLS had predictive value for the detection of abnormal LVEF at 12‐month follow‐up. Thus, myocardial deformation study should be applied early after BMT to prevent irreversible cardiac dysfunction by appropriate treatment. HighlightsWe investigated whether conventional, three‐dimensional, and myocardial deformation echocardiography indices can detect early cardiac dysfunction in patients after bone marrow transplantation.Impaired left and right ventricular global longitudinal strain values were observed from 1 month after bone marrow transplantation and throughout the 12‐month follow‐up period compared to baseline.Compared to baseline, left ventricular ejection fraction was slightly reduced at the end of the follow‐up and left ventricular global longitudinal strain at 1 month after bone marrow transplantation had the strongest predictive value for the identification of abnormal left ventricular ejection fraction at the end of the follow‐up.

TREATMENT WITH ANTI-IL12/23 AGENTS IMPROVES FETUIN AND OXIDATIVE STRESS IN PARALLEL WITH ENDOTHELIAL GLYCOCALYX, CORONARY FUNCTION AND MYOCARDIAL TWISTING IN PATIENTS WITH PSORIASIS

Fetuin inhibits vascular calcification. The effects of biological agents on fetuin, oxidative stress, vascular and LV function in psoriasis is unclear. 101 patients(age:50±12yrs) with psoriasis (PS)were randomized to an anti-TNF-a(n=31),an anti-IL12/23 regimen (n=32)or cyclosporine(n=38).At