Real-time imaging of regional myocardial function using fast-SENC.

A technique for fast imaging of regional myocardial function using a spiral acquisition in combination with strain-encoded (SENC) magnetic resonance imaging (MRI) is presented in this paper. This technique, which is termed fast-SENC, enables scan durations as short as a single heartbeat. A reduced field of view (FOV) without foldover artifacts was achieved by localized SENC, which selectively excited the region around the heart. The two images required for SENC imaging (low- and high-tuning) were acquired in an interleaved fashion throughout the cardiac cycle to further shorten the scan time. Regional circumferential contraction and longitudinal shortening of both the left ventricle (LV) and right ventricle (RV) were examined in long- and short-axis views, respectively. The in vivo results obtained from five human subjects and five infarcted dogs are presented. The results of the fast-SENC technique in a single heartbeat acquisition were comparable to those obtained by conventional SENC in a long acquisition time. Therefore, fast-SENC may prove useful for imaging during stress or arrhythmia.

Effets hémodynamiques d'un inhibiteur de l'effet vasculaire de la vasopressine chez des patients avec insuffisance cardiaque congestive [Hemodynamic effects of an inhibitor of the vascular effects of vasopressin in patients with congestive heart failure]

To assess the role of vasopressin (AVP) in congestive heart failure (CHF), we investigated 10 patients with CHF refractory to conventional treatment, before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution, and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients there was no significant hemodynamic and cutaneous blood flow response to the AVP antagonist. Plasma AVP was 2.3 +/- 0.8 pg/ml and plasma osmolality 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP was 55 pg/ml and plasma osmolality 290 mosm/kg. He responded to the AVP antagonist with a marked decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously cardiac index increased from 1.1 to 2.21 X min-1 X m-2 and cutaneous blood flow rose 5-fold. Thus, most patients with CHF have only moderately elevated plasma AVP and its role in determining peripheral vascular resistance appears to be limited. AVP may become important in rare patients presenting with marked hemodynamic instability and very high plasma AVP.

Dietary fish oil is antihypertrophic but does not enhance postischemic myocardial function in female mice.

Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid (PUFA) cardioprotection in females has not been clearly established. The goal of this study was to investigate whether dietary omega-3 PUFA supplementation could provide ischemic protection in female mice with an underlying genetic predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with cardiac-specific overexpression of angiotensinogen that develop normotensive cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil-derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial membrane lipids, ex vivo cardiac performance (intraventricular balloon) after global no-flow ischemia and reperfusion (15/30 min), and reperfusion arrhythmia incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT and TG, respectively (P < 0.001). The extent of mechanical recovery [rate-pressure product (RPP) = beats/min x mmHg] of FO-fed WT and TG hearts was similar (50 +/- 7% vs. 45 +/- 12%, 30 min reperfusion), and this was not significantly different from CTR-fed WT or TG. To evaluate whether systemic estrogen was masking a protective effect of the FO diet, the responses of ovariectomized (OVX) WT and TG mice to FO dietary intervention were assessed. The extent of mechanical recovery of FO-fed OVX WT and TG (RPP, 50 +/- 4% vs. 64 +/- 8%) was not enhanced compared with CTR-fed mice (RPP, 60 +/- 11% vs. 80 +/- 8%, P = 0.335). Dietary FO did not suppress the incidence of reperfusion arrhythmias in WT or TG hearts (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective effect of dietary FO in females, determined by assessment of mechanical and arrhythmic activity postischemia in a murine ex vivo heart model.

Reversible congestive heart failure associated with primary carnitin deficiency: report of a case and review of the literature.

A 5-year-old previously healthy boy was admitted for abdominal pain and vomiting. Physical examination showed tachypnoe (32/min), hepatomegaly and painful palpation of the upper right abdominal quadrant. Laboratory tests were normal except for elevated ammonium (202mcmol/l). Chest X-ray was performed, showing cardiomegaly and interstitial edema. Transthoracic echocardiography revealed dilated left cavities and LV hypertrophy together with a diffuse hypokinesia and LVEF of 30-40%. Diuretics and ACE-inhibitors were introduced. At that time, the differential diagnosis for the DCM included myocarditis, congenital or genetic, metabolic or autoimmune disease. The next day, the boy underwent cardiac magnetic resonance (CMR) examination, showing a severe dilatation of the LV with an end-diastolic diameter of 50mm and a volume of 150ml. LVEF was 20% with diffuse LV hypokinesia (Fig. 1). No late enhancement was present after Gadolinium injection, ruling out myocarditis. Further laboratory metabolic analysis indicated severely decreased total and free carnitin levels and low renal carnitin reabsorption, corroborating the diagnosis of primary carnitin deficiency (PCD). Carnitin substitution was initiated. The clinical condition rapidly improved. No symptoms of heart failure were present anymore. A follow-up CMR performed 9 months later confirmed the recovery. LV end-diastolic volume decreased from 150ml to 66ml, LVEF increased from 20% to 55% (Fig. 2). Late enhancement was absent after Gadolinum injection (Fig. 3).Carnitin is required for the transport of fatty acids from the cytosol into mitochondria during lipid breakdown. 75% of carnitin is obtained from food, 25% is endogenously synthesized. PCD is an autosomal recessive disorder resulting from impairment of a transporter activity, caused by mutation of the SLC22A5 gene. Incidence is about 1 in 40'000 newborns. Diagnosis is usually made at age 1 to 7. Three forms of PCD are described. In the form associated with cardiomyopathy, the disease is progressive and patient die from heart failure if not treated. Substitution of L-Carnitin leads to a dramatic improvement of disease course.This case underlines the crucial role of etiologic diagnostics in this reversible form of DCM. Early diagnostics and therapy are critical for the prognosis of the patient. This is furthermore an example of a role played by CMR in the diagnostic work-up of heart failure and its follow-up under therapy.

Confounding effects of heart rate on pulse wave velocity in paced patients with a low degree of atherosclerosis.

BACKGROUND: Pulse wave velocity (PWV), an index of arterial wall stiffness, is modulated by blood pressure (BP). Whether heart rate (HR) is also a modulator of PWV is controversial. Recent research involving mainly patients with high aortic PWV have found either no change or a positive correlation between the two. Given that PWV is increasingly being measured in cardiovascular studies, the relationship between HR and PWV should be known in patients with preserved arterial wall elasticity. OBJECTIVE: The aim of this study was to evaluate the importance of HR as a determinant of the variability in PWV in patients with a low degree of atherosclerosis. DESIGN AND METHODS: Fourteen patients (five female, nine male; aged 68 +/- 8 years) were evaluated post pacemaker implantation due to sick sinus or carotid hypersensitivity syndromes. Carotid-femoral PWV was measured at rest and during atrial pacing at 80, 90 and 100 bpm (paced HR). Arterial femoral blood flow (AFBF) was measured by echodoppler. RESULTS: PWV increased from 6.2 +/- 1.5 m/s (mean +/- SD) during resting sinus rhythm (HR 62 +/- 8 bpm; mean +/- SD) to 6.8 +/- 1.0, 7.0 +/- 0.9, and 7.6 +/- 1.1 m/s at pacing rates of 80, 90 and 100 bpm, respectively (P < 0.0001). Systolic (SBP) and mean blood pressure (MBP) remained constant at all HR levels, whereas AFBF increased in a linear fashion. CONCLUSIONS: These results demonstrate that even in patients with a low degree of atherosclerosis, HR is a potential modulator of carotid-femoral PWV.

Postinfarction heart failure in rats is associated with upregulation of GLUT-1 and downregulation of genes of fatty acid metabolism.

OBJECTIVES: Increasing evidence suggests that left ventricular remodeling is associated with a shift from fatty acid to glucose metabolism for energy production. The aim of this study was to determine whether left ventricular remodeling with and without late-onset heart failure after myocardial infarction is associated with regional changes in the expression of regulatory proteins of glucose or fatty acid metabolism. METHODS: Myocardial infarction was induced in rats by ligation of the left anterior descending coronary artery (LAD). In infarcted and sham-operated hearts the peri-infarction region (5-mm zone surrounding the region at risk), the interventricular septum and the right ventricular free wall were separated for analysis. RESULTS: At 8 and 20 weeks after LAD ligation, the peri-infarction region and the septum exhibited marked re-expression of atrial natriuretic factor [+252+/-37 and +1093+/-279%, respectively, in the septum (P<0.05)] and of alpha-smooth muscle actin [+34+/-10 and +43+/-14%, respectively, in the septum (P<0.05)]. At 8 weeks, when left ventricular hypertrophy was present without signs of heart failure, myocardial mRNA expression of glucose transporters (GLUT-1 and GLUT-4) was not altered, whereas mRNA expression of medium-chain acyl-CoA dehydrogenase (MCAD) was significantly reduced in the peri-infarction region (-25+/-7%; P<0.05). In hearts exhibiting heart failure 20 weeks after infarct-induction there was a change in all three ventricular regions of both mRNA and protein content of GLUT-1 [+72+/-28 and +121+/-15%, respectively, in the peri-infarction region (P<0.05)] and MCAD [-29+/-9 and -56+/-4%, respectively, in the peri-infarction region (P<0.05)]. CONCLUSION: In rats with large myocardial infarction, progression from compensated remodeling to overt heart failure is associated with upregulation of GLUT-1 and downregulation of MCAD in both the peri-infarction region and the septum.

Involvement of CD73, equilibrative nucleoside transporters and inosine in rhythm and conduction disturbances mediated by adenosine A1 and A2A receptors in the developing heart.

We previously established that exogenous adenosine (ADO) induces transient arrhythmias in the developing heart via the adenosine A1 receptor (A1AR) and downstream activation of NADPH oxidase/ERK and PLC/PKC pathways. Here, we investigated the mechanisms by which accumulation of endogenous ADO and its derived compound inosine (INO) in the interstitial compartment induce rhythm and conduction troubles. The validated model of the spontaneously beating heart obtained from 4-day-old chick embryos was used. Quantitative RT-PCR showed that enzymes involved in ADO and INO metabolism (CD39, CD73 and eADA) as well as equilibrative (ENT1, -3, -4) and concentrative (CNT3) nucleoside transporters were differentially expressed in atria, ventricle and outflow tract. Inactivation of ENTs by dipyridamole, 1) increased myocardial ADO level, 2) provoked atrial arrhythmias and atrio-ventricular blocks (AVB) in 70% of the hearts, 3) prolonged P wave and QT interval without altering contractility, and 4) increased ERK2 phosphorylation. Blockade of CD73-mediated phosphohydrolysis of AMP to ADO, MEK/ERK pathway inhibition or A1AR inhibition prevented these arrhythmias. Exposure to exogenous INO also caused atrial ectopy associated with AVB and ERK2 phosphorylation which were prevented by A1AR or A2AAR antagonists exclusively or by MEK/ERK inhibitor. Inhibition of ADA-mediated conversion of ADO to INO increased myocardial ADO and decreased INO as expected, but slightly augmented heart rate variability without provoking AVB. Thus, during cardiogenesis, disturbances of nucleosides metabolism and transport, can lead to interstitial accumulation of ADO and INO and provoke arrhythmias in an autocrine/paracrine manner through A1AR and A2AAR stimulation and ERK2 activation.

Suivi du patient après transplantation cardiaque: monitoring et adaptation de l'immunosuppression [Monitoring and adjustment of immunosuppression after heart transplantation].

Heart transplantation remains the best therapeutic option for the treatment of end-stage heart failure. However, good survival rates can be obtained only if patients are closely monitored, particularly for their immunosuppressive regimens. Currently, a triple-drug regimen usually based on calcineurin-inhibitors (cyclosporin A or tacrolimus), anti-proliferative agents and steroids is used in most recipients. New agents such as the mTOR inhibitors, a more recently developed class of immunosuppressive drugs, can also be used in some patients. The aim of this article is to review currently used immunosuppressive regimens after heart transplantation, and to propose some individualized options depending on specific patient characteristics and recent pharmacological developments in the field.

The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.

Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hypertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload.

Free-breathing inner-volume black-blood imaging of the human heart using two-dimensionally selective local excitation at 3 T.

Black-blood fast spin-echo imaging is a powerful technique for the evaluation of cardiac anatomy. To avoid fold-over artifacts, using a sufficiently large field of view in phase-encoding direction is mandatory. The related oversampling affects scanning time and respiratory chest motion artifacts are commonly observed. The excitation of a volume that exclusively includes the heart without its surrounding structures may help to improve scan efficiency and minimize motion artifacts. Therefore, and by building on previously reported inner-volume approach, the combination of a black-blood fast spin-echo sequence with a two-dimensionally selective radiofrequency pulse is proposed for selective "local excitation" small field of view imaging of the heart. This local excitation technique has been developed, implemented, and tested in phantoms and in vivo. With this method, small field of view imaging of a user-specified region in the human thorax is feasible, scanning becomes more time efficient, motion artifacts can be minimized, and additional flexibility in the choice of imaging parameters can be exploited.

Whole-heart coronary vein imaging: a comparison between non-contrast-agent- and contrast-agent-enhanced visualization of the coronary venous system.

The feasibility of three-dimensional (3D) whole-heart imaging of the coronary venous (CV) system was investigated. The hypothesis that coronary magnetic resonance venography (CMRV) can be improved by using an intravascular contrast agent (CA) was tested. A simplified model of the contrast in T(2)-prepared steady-state free precession (SSFP) imaging was applied to calculate optimal T(2)-preparation durations for the various deoxygenation levels expected in venous blood. Non-contrast-agent (nCA)- and CA-enhanced images were compared for the delineation of the coronary sinus (CS) and its main tributaries. A quantitative analysis of the resulting contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) in both approaches was performed. Precontrast visualization of the CV system was limited by the poor CNR between large portions of the venous blood and the surrounding tissue. Postcontrast, a significant increase in CNR between the venous blood and the myocardium (Myo) resulted in a clear delineation of the target vessels. The CNR improvement was 347% (P < 0.05) for the CS, 260% (P < 0.01) for the mid cardiac vein (MCV), and 430% (P < 0.05) for the great cardiac vein (GCV). The improvement in SNR was on average 155%, but was not statistically significant for the CS and the MCV. The signal of the Myo could be significantly reduced to about 25% (P < 0.001).

Simultaneous B(0)- and B(1)+-map acquisition for fast localized shim, frequency, and RF power determination in the heart at 3 T.

High-field (>or=3 T) cardiac MRI is challenged by inhomogeneities of both the static magnetic field (B(0)) and the transmit radiofrequency field (B(1)+). The inhomogeneous B fields not only demand improved shimming methods but also impede the correct determination of the zero-order terms, i.e., the local resonance frequency f(0) and the radiofrequency power to generate the intended local B(1)+ field. In this work, dual echo time B(0)-map and dual flip angle B(1)+-map acquisition methods are combined to acquire multislice B(0)- and B(1)+-maps simultaneously covering the entire heart in a single breath hold of 18 heartbeats. A previously proposed excitation pulse shape dependent slice profile correction is tested and applied to reduce systematic errors of the multislice B(1)+-map. Localized higher-order shim correction values including the zero-order terms for frequency f(0) and radiofrequency power can be determined based on the acquired B(0)- and B(1)+-maps. This method has been tested in 7 healthy adult human subjects at 3 T and improved the B(0) field homogeneity (standard deviation) from 60 Hz to 35 Hz and the average B(1)+ field from 77% to 100% of the desired B(1)+ field when compared to more commonly used preparation methods.

Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death.

BACKGROUND: Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. METHODS: We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and > or = 10.0 mIU/L). RESULTS: Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of > or = 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure.