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We assessed the effects of intracoronary administration of substance P, LNMMA, L-arginine, and nitroglycerin in patients with normal coronary angiograms and in patients with coronary artery disease. LNMMA constricted (p <0.01) and both substance P and nitroglycerin dilated normal and diseased proximal and distal segments and stenoses (p <0.01). L-Arginine reversed the effect of LNMMA in all segments and caused greater dilation of the diseased arteries, including stenoses (p <0.05), indicating that there is a relative deficiency of L-arginine in diseased coronary arteries. [ABSTRACT FROM AUTHOR]

Background and Aims: Increased β-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization., Patients and Methods: In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) β-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up., Results: Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with β-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, β-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and β-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and β-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD., Conclusions: Increased β-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.

Purpose: In the current case series, we present our experience with the self-expanding CoreValve or Evolut R (Medtronic Inc.) in patients with severe symptomatic aortic valve stenosis and concomitant mitral valve prosthesis., Methods: Twelve patients with previous mitral valve prosthesis underwent transcatheter aortic valve replacement for severe symptomatic aortic valve stenosis and/or aortic valve regurgitation. All patients underwent evaluation with an echocardiogram, computed tomography and coronary angiogram. After the index intervention and before discharge all patients underwent transthoracic echocardiography. All outcomes were defined according to the Valve Academic Research Consortium-2 criteria., Results: Eleven patients underwent transcatheter aortic valve replacement for severe symptomatic aortic valve stenosis and one patient for severe aortic valve regurgitation. There was immediate improvement of patients' hemodynamic status; no cases of procedural death, stroke, myocardial infarction, or urgent cardiac surgery occurred. There was no 30-day mortality and all patients improved, with 91.6% in functional New York Heart Association class I-II., Conclusion: The current study demonstrates that in patients with severe aortic valve stenosis or regurgitation and mitral valve prosthesis, the implantation of a self-expanding aortic valve via the transfemoral route is safe and feasible, with maintained long-term results.

Angiotensin converting enzyme (ACE) promotes cardiac fibrosis. LV myocardial deformation and torsion are markers of subclinical myocardial dysfunction. We investigated the association of serum ACE levels with LV deformation markers in untreated hypertensives. In 120 untreated patients (age: 53.5 ± 11.2 years) with essential hypertension and 60 healthy controls, we measured (a) LV longitudinal, circumferential and radial strain (S), peak torsion and the percentage changes between peak twisting and untwisting at the end of early diastolic filling (%dpTw-Utw EDF ) using speckle tracking echocardiography and (b) serum levels of ACE and NTproBNP. Compared to controls, patients had decreased longitudinal strain (-19.1 ± 2.9 vs. -21.7 ± 1.8%), increased peak twisting (19.1 ± 4.6 vs.14.0 ± 3.7 deg) but decreased %dpTw-Utw EDF (78 ± 8 vs. 86 ± 8%) and higher serum ACE levels (27.6 ± 8.0 vs 20.9 ± 7.1 U/ml) (p < 0.05 for all comparisons). Increasing serum ACE levels were related to impaired radial strain and longitudinal systolic SR (b = -0.41 and b = 0.31 respectively, p < 0.01), as well as to reduced %dpTw-Utw EDF (b = -0.37, p < 0.05). Furthermore, increasing serum ACE levels were related to increasing NTproBNP levels (b = 0.41, p < 0.01). In multivariate analysis, the above relations of serum ACE levels and LV function parameters remained significant after adjustment for other confounding factors (p < 0.01). The close link between serum ACE levels and impaired LV deformation suggests that activation of renin-angiotensin system is involved in the impairment of LV function resulting in elevated LV filling pressures causing the concomitant elevation of BNP levels in untreated hypertensive patients.

Aim: To investigate the association of arterial wave reflection with coronary flow reserve (CFR) in coronary artery disease (CAD) patients after successful revascularization., Methods: We assessed 70 patients with angiographically documented CAD who had undergone recent successful revascularization. We measured (1) reactive hyperemia index (RHI) using fingertip peripheral arterial tonometry (RH-PAT Endo-PAT); (2) carotid to femoral pulse wave velocity (PWVc-Complior); (3) augmentation index (AIx), the diastolic area (DAI%) and diastolic reflection area (DRA) of the central aortic pulse wave (Arteriograph); (4) CFR using Doppler echocardiography; and (5) blood levels of lipoprotein-phospholipase A2 (Lp-PLA2)., Results: After adjustment for age, sex, blood pressure parameter, lipidemic, diabetic and smoking status, we found that coronary flow reserve was independently related to AIx (b = -0.38, r = 0.009), DAI (b = 0.36, P = 0.014), DRA (b = 0.39, P = 0.005) and RT (b = -0.29, P = 0.026). Additionally, patients with CFR < 2.5 had higher PWVc (11.6 ± 2.3 vs 10.2 ± 1.4 m/s, P = 0.019), SBPc (139.1 ± 17.8 vs 125.2 ± 19.1 mmHg, P = 0.026), AIx (38.2% ± 14.8% vs 29.4% ± 15.1%, P = 0.011) and lower RHI (1.26 ± 0.28 vs 1.50 ± 0.46, P = 0.012), DAI (44.3% ± 7.9% vs 53.9% ± 6.7%, P = 0.008), DRA (42.2 ± 9.6 vs 51.6 ± 11.4, P = 0.012) and LpPLA2 (268.1 ± 91.9 vs 199.5 ± 78.4 ng/mL, P = 0.002) compared with those with CFR ≥ 2.5. Elevated LpPLA2 was related with reduced CFR (r = -0.33, P = 0.001), RHI (r = -0.37, P < 0.001) and DRA (r = -0.35, P = 0.001) as well as increased PWVc (r = 0.34, P = 0.012) and AIx (r = 0.34, P = 0.001)., Conclusion: Abnormal arterial wave reflections are related with impaired coronary flow reserve despite successful revascularization in CAD patients. There is a common inflammatory link between impaired aortic wall properties, endothelial dysfunction and coronary flow impairment in CAD.

Background: The effect of raloxifene on aortic elasticity in healthy postmenopausal women is unknown. The purpose of the present study was to examine the effect of raloxifene on aortic elasticity and cardiovascular structure and function in healthy postmenopausal women., Methods: A randomized, crossover, double-blind, placebo-controlled clinical trial was performed. Fourteen healthy postmenopausal women received treatment with raloxifene 60 mg daily and matching placebo for 8 weeks with an 8-week washout period in between the 2 treatment periods. Cardiovascular magnetic resonance imaging was used to assess ascending thoracic and abdominal aortic elasticity and cardiovascular structure and function (left ventricular volumes, ejection fraction, and mass and mitral annular displacement) before and at the end of each treatment period., Results: Administration of raloxifene had no significant effect on either heart rate or systemic blood pressure. Raloxifene treatment was associated with a small decrease of the ascending aorta wall thickness (pretreatment 2.4 +/- 0.3 vs posttreatment 2.2 +/- 0.2 mm, P = .01). Consequently, there was an increase in the Young's elastic modulus after raloxifene treatment at the ascending thoracic aorta but not the abdominal aorta. There were no significant differences in aortic compliance or any cardiac indexes after raloxifene treatment., Conclusions: Raloxifene administration in healthy postmenopausal women over an 8-week period may decrease the aortic wall thickness but has no significant effects on aortic compliance or cardiac structure and function.

Purpose: To address degradation of coronary MR angiography (MRA) image quality due to heart rate variability (HRV)-associated variations in coronary artery position and motion., Materials and Methods: Free-breathing navigator-gated and -corrected coronary MRA using subject-specific trigger delays and acquisition windows was combined with a real-time HRV correction algorithm, such as commonly used in left ventricular wall motion studies. Ten healthy adults underwent free-breathing navigator-gated and -corrected coronary MRA with and without HRV correction. Signal-to-noise (SNR), contrast-to-noise (CNR), vessel length, diameter, sharpness, and subjective image quality (on a five-point scale) were compared in a blinded fashion., Results: Vessel sharpness improved significantly for both the left (LCA) and right (RCA) coronary artery systems (P = 0.016 and P = 0.015, respectively) with the use of HRV correction. Subjective image quality also improved significantly when HRV correction was used (P = 0.003). There were no significant differences with regard to SNR and CNR (P > 0.1)., Conclusions: Preliminary results suggest that HRV correction improves objective and subjective image quality in coronary MRA. Continued studies in patients with known or suspected coronary artery disease are warranted to investigate the clinical impact of this technique., ((c) 2005 Wiley-Liss, Inc.)

Left atrial (LA) volume is associated with cardiovascular morbidity, particularly atrial fibrillation. Contrast-enhanced magnetic resonance angiography (CE-MRA) visualizes the LA, but the validity of LA volume measurements using this technique has not been evaluated. We performed CE-MRA and cine magnetic resonance (MR) in 18 consecutive patients referred for CE-MRA prior to atrial fibrillation ablation. The CE-MRA LA volumes were compared to cine MR LA volumes at the maximal LA size and at LA end-diastole using linear regression and limits of agreement analysis. The mean cine MR LA volume was 118 +/- 39 mL at maximal LA size and 91 +/- 38 mL at LA end-diastole. Left atrial volume determined by CE-MRA was 93 +/- 38 mL. Although the CE-MRA LA volume had a strong correlation with the maximal cine MR LA volume (R2 = 0.86, p < 0.001), the 95% limits of agreement were relatively wide (-54 to 3 mL). The cine MR LA end-diastolic and CE-MRA LA volumes were more closely correlated (R2 = 0.98, p < 0.001) with narrow 95% limits of agreement (-8 to 11 mL). The CE-MRA LA volumes correspond most closely to LA end-diastolic cine MR LA volumes and may be a useful measure of LA size.

Objectives: We sought to develop a reproducible method for characterizing the anatomy of the proximal pulmonary veins., Background: Contrast-enhanced three-dimensional magnetic resonance angiography (CE-MRA) is a commonly requested test before and after radiofrequency ablation for the treatment of atrial fibrillation. While CE-MRA readily visualizes the pulmonary veins, there is no standardized method for determining their size and cross-sectional anatomy., Methods: Data for 24 consecutive patients referred for pulmonary vein CE-MRA before an elective ablation procedure for the treatment of atrial fibrillation were analyzed. Detailed measurements of the pulmonary vein diameter, circumference, and cross-sectional area were obtained at three locations: the juncture of the pulmonary vein with the left atrium (LA) (position 1J), the narrowest segment within 5 mm of the juncture (position 2(5mm)), and at the location in the sagittal plane at which the pulmonary veins separate from the LA and from each other (position 3Sag). Intraobserver and interobserver variabilities were also determined for each method., Results: The left lower pulmonary vein was significantly smaller than the other pulmonary veins at positions 1J and 2(5mm) (p<0.05). The right upper pulmonary vein was significantly larger than the other pulmonary vein at position 3Sag (p<0.05). At positions 1J and 2(5mm), the diameter had a low correlation with the circumference and cross-sectional area. At position 3Sag, the major and minor axis dimensions had a very high correlation with the circumference and cross-sectional area. The intraobserver and interobserver variabilities were substantially lower (better) for position 3Sag., Conclusions: Pulmonary vein diameter measurements are highly variable and do not reflect true anatomic variation in cross-sectional anatomy. A sagittal method of determining pulmonary vein size was highly reproducible and may therefore be advantageous for use in patients likely to need serial examinations.

Coronary magnetic resonance angiography (CMRA) is a technique in clinical evolution. Current clinical applications include assessment for coronary anomalies, aneurysms, bypass graft patency, and, in experienced centers, the exclusion of proximal and multivessel coronary artery disease (CAD). As local expertise increases and more extensive multicenter data become available, additional applications will be established. CMRA promises to supplement and in some cases obviate the need for X-ray contrast angiography, and to expand our understanding of the pathophysiology of CAD.