Abstract: BACKGROUND: Both low free triiodothyronine (fT3) and high brain natriuretic peptide (BNP) have been separately described as prognostic predictors for mortality in heart failure (HF). We investigated whether their prognostic value is independent. METHODS AND RESULTS: From January of 2001 to December of 2006, we prospectively evaluated 442 consecutive patients with systolic HF and no thyroid disease or treatment with drugs affecting thyroid function (age 65+/-12 years, mean +/- standard deviation, 75% were male, left ventricular ejection fraction 33% +/- 10%, New York Heart Association (NYHA) class I and II: 63%, NYHA class III and IV: 37%). All patients underwent full clinical and echocardiographic evaluation and assessment of BNP and thyroid function. Both cardiac and all-cause mortality (cumulative) were considered as end points. During a median 36-month follow-up (range 1-86 months), 110 patients (24.8%) died, 64 (14.4%) of cardiac causes. Univariate Cox model predictors of all-cause mortality and cardiac death were age, body mass index, creatinine, hemoglobin, ejection fraction, NYHA class, BNP, fT3, and thyroxine level. Multivariate analysis selected age, NYHA class, hemoglobin, BNP, and fT3 as independent predictors for all-cause mortality and NYHA class, BNP, and fT3 as independent predictors for cardiac mortality. Patients with low fT3 and higher BNP showed the highest risk of all-cause and cardiac death (odds ratio 11.6, confidence interval, 5.8-22.9; odds ratio 13.8, confidence interval, 5.4-35.2, respectively, compared with patients with normal fT3 and low BNP). CONCLUSION: fT3 and BNP hold an independent and additive prognostic value in HF.

Abstract: Mild-to-moderate hypertension is often associated with insulin resistance and visceral adiposity. Whether these metabolic abnormalities have an independent impact on regional cardiac function is not known. The goal of this study was to investigate the effects of increased blood pressure, insulin resistance, and ectopic fat accumulation on the changes in peak systolic circumferential strain. Thirty-five male subjects (age: 47+/-1 years; body mass index: 28.4+/-0.6 kg m(-2); mean+/-SEM) included 13 with normal blood pressure (BP: 113+/-5/67+/-2 mm Hg), 13 with prehypertension (BP: 130+/-1/76+/-2 mm Hg), and 9 newly diagnosed with essential hypertension (BP: 150+/-2/94+/-2 mm Hg) who underwent cardiac magnetic resonance tissue tagging (MRI) and MRI quantitation of abdominal visceral and epicardial fat. Glucose tolerance, on oral glucose tolerance test, and insulin resistance were assessed along with the serum lipid profile. All of the subjects had normal glucose tolerance, left- and right-ventricular volumes, and ejection fraction. Across the BP groups, left ventricular mass tended to increase, and circumferential shortening was progressively reduced at basal, midheart, and apical segments (on average, from -17.0+/-0.5% in normal blood pressure to -15.2+/-0.7% in prehypertension to -13.6+/-0.8% in those newly diagnosed with essential hypertension; P=0.004). Reduced circumferential strain was significantly associated with raised BP independent of age (r=0.41; P=0.01) and with epicardial and visceral fat, serum triglycerides, and insulin resistance independent of age and BP. In conclusion, regional left ventricular function is already reduced at the early stages of hypertension despite the normal global cardiac function. Insulin resistance, dyslipidemia, and ectopic fat accumulation are associated with reduced regional systolic function.

Abstract: CONTEXT: Low-T(3) syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T(3) replacement therapy in patients with low-T(3) syndrome and ischemic or nonischemic dilated cardiomyopathy (DC). DESIGN: A total of 20 clinically stable patients with ischemic (n = 12) or nonischemic (n = 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66-77; median, 25-75th percentile) who underwent 3-d synthetic L-T(3) infusion (study group); the other 10 patients (average age 68 yr, range 64-71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T(3) (initial dose: 20 microg/m(2) body surface.d) or placebo infusion. RESULTS: After T(3) administration, free T(3) concentrations increased until reaching a plateau at 24-48 h (3.43, 3.20-3.84 vs. 1.74, 1.62-1.93 pg/ml; P = 0.03) without side effects. Heart rate decreased significantly after T(3) infusion (63, 60-66 vs. 69, 60-76 beats per minute; P = 0.008). Plasma noradrenaline (347; 270-740 vs. 717, 413-808 pg/ml; P = 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P = 0.02), and aldosterone (175, 152-229 vs. 231, 154-324 pg/ml; P = 0.047) significantly decreased after T(3) administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T(3) administration, left-ventricular end-diastolic volume (142, 132-161 vs. 133, 114-158 ml/m(2) body surface; P = 0.02) and stroke volume (40, 34-44 vs. 35, 28-39 ml/m(2) body surface; P = 0.01) increased, whereas external and intracardiac workload did not change. CONCLUSIONS: In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T(3) administration.

Abstract: Interest in the role of thyroid hormones (TH) in heart failure is steadily increasing due to evidence for a physiological, homeostatic role of TH and the effects of altered TH metabolism on the cardiovascular system, particularly in presence of heart failure. Experimental studies have shown that altered TH metabolism modifies cardiovascular homeostasis by inducing alterations of cardiac histology, cardiomyocyte morphology and gene expression and consequently, of diastolic and systolic myocardial function. Clinical studies have shown that mild forms of thyroid dysfunction, both primary (subclinical hypothyroidism and subclinical hyperthyroidism) and secondary (low T(3) syndrome) have negative prognostic impact in patients with heart failure. In these patients, the administration of synthetic triiodothyronine (T(3)) was well tolerated and induced significant improvement in cardiac function without increased heart rate and metabolic demand. Large multicenter, placebo-controlled prospective studies are necessary to evaluate the safety and prognostic effects of chronic treatment with TH replacement therapy in patients with heart failure. The article also discusses recent patents in this field.

Abstract: Prolonged breath hold (BH) represents a valid model for studying the cardiac adaptation to acute hypoxemia in humans. Cardiac magnetic resonance (CMR) allows a three-dimensional, high-resolution, noninvasive, and nonionizing anatomical and functional evaluation of the heart. The aim of the study was to assess the adaptation of the cardiovascular system to prolonged BH in air. Ten male volunteer diving athletes (age 30 +/- 6 yr) were studied during maximal BH duration with CMR. Four epochs were studied: I, rest; II and III, intermediate BH; and IV, peak BH. Oxygen saturation (So(2)), heart rate (HR), blood pressure (BP), systemic vascular resistance (VR), end-diastolic (EDV) and end-systolic volumes (ESV), stroke volume (SV), cardiac output (CO), ejection fraction (EF), maximal elastance index (EL), systolic wall thickening (SWT), and end-systolic wall stress (ESWS) of the left ventricle (LV) were measured in all four BH epochs. Average BH duration was 3.7 +/- 0.3 min. So(2) was reduced (I: 97 +/- 0.2%, range 96-98%, vs. IV: 84 +/- 2.0%, range 76-92%; P < 0.00001). BP, EDV, ESV, SV, CO, and ESWS linearly increased from epochs I to IV, whereas EF, EL, and SWT showed an opposite behavior, decreasing from resting to epoch IV (all trends are P < 0.01). During prolonged BH in air, a marked enlargement of the LV chamber occurs in healthy diving athletes. This response to acute hypoxemia allows SV,CO, and arterial pressure to be maintained despite the severe reduction in LV contractile function.

Abstract: The aim of this study was to compare the diagnostic accuracy of perfusion and wall motion (WM) during dipyridamole magnetic resonance in patients with chest pain syndrome. Ninety-three patients with normal baseline left ventricular function were referred for coronary angiography. Additional dipyridamole stress magnetic resonance testing (0.84 mg/kg over 6 minutes; using a Signa Cvi scanner) was performed. Cardiac-gated fast gradient-echo train sequences with a first pass of gadolinium contrast medium were used to assess myocardial perfusion. A perfusion reserve index was calculated as the ratio of dipyridamole to rest upslope. A perfusion reserve index value <1.54 in 2 contiguous myocardial segments was the perfusion positivity criterion. The WM positivity criterion was a segmental score increase of > or =1 grade in > or =2 segments. WM and the perfusion reserve index showed similar diagnostic accuracy for >50% quantitatively assessed coronary diameter reduction (86% for both), with WM having higher specificity (96% vs 66%, p <0.01) and lower sensitivity (82% vs 93%, p <0.05) than the perfusion reserve index. Perfusion had the highest accuracy values for coronary stenoses <75% (cutoff 59%) and WM for coronary stenoses > or =75% (cutoff 84%) (p <0.001). In conclusion, during dipyridamole magnetic resonance stress testing, perfusion and WM abnormalities have similar diagnostic accuracy, with perfusion showing higher sensitivity, particularly in the detection of moderate stenoses, and WM showing higher specificity.

Abstract: Thyroid hormone (TH) has a fundamental role in cardiovascular homeostasis in both physiological and pathological conditions, influencing cardiac contractility, heart rate (HR), diastolic function and systemic vascular resistance (SVR) through genomic and non-genomic mediated effects. In heart failure (HF) the main alteration of thyroid function is referred to as "low-triiodothyronine (T3) syndrome" (LT3S) characterized by decreased total serum T3 and free T3 (fT3) with normal levels of thyroxine (T4) and thyrotropin (TSH). Even if commonly interpreted as an adaptive factor, LT3S may have potential negative effects, contributing to the progressive deterioration of cardiac function and myocardial remodeling in HF and representing a powerful predictor of mortality in HF patients. All these observations, together with the early evidence of the benefits of T3 administration in HF patients indicate that placebo-controlled prospective studies are now needed to better define the safety and prognostic effects of chronic treatment with synthetic TH in HF.

Abstract: BACKGROUND: After acute myocardial infarction (MI) the severity of diastolic dysfunction by echocardiography represents an independent prognostic marker. However, the mechanisms whereby diastolic dysfunction portends an increased risk after MI are not fully understood. We investigated the relationship between echocardiographic diastolic dysfunction severity and infarct size quantitatively measured by contrast-enhanced magnetic resonance (ce-MR). METHODS: Cross-sectional prospective study. We quantified "healed" infarct size by ce-MR measuring the percentage of delayed enhancement with respect to left ventricular mass and diastolic function by Doppler echocardiography. Both exams were scheduled at least 1 month after a first acute ST segment elevation MI (STEMI) successfully treated with primary angioplasty and stenting. To increase the specificity, individual echocardiographic parameters were integrated to grade global diastolic function in 4 grades: normal diastolic function, impaired relaxation with normal, or near-normal filling pressures; impaired relaxation with moderate elevation of filling pressures, and impaired relaxation with marked elevation of filling pressures, "restrictive filling." RESULTS: We prospectively enrolled 52 patients (mean age 62 +/- 13 years, 77% men). ce-MR and echocardiography were performed 48 +/- 15 days after the MI. There was a significant but modest correlation between diastolic function grade and infarct size (r = 0.423, P = 0.002), which was independent of global and regional systolic function and persisted after further adjustment for age, sex, body surface area, left ventricular mass, end-diastolic volumes, and sphericity index (all P < 0.05). Among single echocardiographic variables, infarct size correlated best with tissue Doppler velocities Em (r =-0.307, P = 0.03), Am (r =-0.39, P = 0.005), and flow propagation velocity (r =-0.34, P = 0.015). CONCLUSIONS: In healed STEMI successfully treated with primary angioplasty and stenting, diastolic function grade was independently albeit weakly correlated with infarct size. Therefore, the increased risk of diastolic dysfunction after MI is not fully explained by infarct size.

Abstract: BACKGROUND: Ultrasound lung comets (ULCs) detected by chest sonography are a simple, noninvasive, semiquantitative sign of increased extravascular lung water. Pulmonary edema may occur in elite apnea divers, possibly triggered by centralization of blood flow from the periphery to pulmonary vessels. We assessed the prevalence of ULCs in top-level breath-hold divers after immersion. METHODS: We evaluated 31 consecutive healthy, top-level, breath-hold divers (10 female, 21 male; age 31 +/- 5 years) participating in a yearly international apnea diving contest in Sharm-el-Sheik, Egypt, November 1 to 3, 2007. We performed chest and cardiac sonography with a transthoracic probe (2.5-3.5 MHz, Esaote Mylab) in all divers, both on the day before and 10 +/- 9 minutes after immersion. In a subset of 4 divers, chest scan was also repeated at 24 hours after immersion. ULCs were evaluated on the anterior and posterior chest at 61 predefined scanning sites. An independent sonographer, blind to both patient identity and status (pre- or post-diving), scored ULCs. RESULTS: Diving depth ranged from 31 to 112 m. Duration of immersion ranged from 120 to 225 seconds. The ULC score was 0.5 +/- 1.5 at baseline and 13 +/- 21 after diving (P = .012). At individual patient analysis, ULCs appeared in 14 athletes (45%) after diving. Of these 14 athletes, 4 were asymptomatic, 6 showed aspecific symptoms with transient loss of motor control ("Samba"), 2 had palpitations with frequent premature ventricular contractions, and 2 had persistent cough with hemoptysis and pulmonary crackles. In a subset of 4 athletes with post-diving ULCs in whom late follow-up study also was available, chest sonography findings fully normalized at 24 hours of follow-up. CONCLUSION: In top-level breath-hold divers, chest sonography frequently reveals an increased number of ULCs after immersion, indicating a relatively high prevalence of (often subclinical) reversible extravascular lung water accumulation.

Abstract: INTRODUCTION: The added value of routine echocardiography, in respect to clinical examination and ECG, has received little attention. We sought to evaluate the contribution of two-dimensional echocardiography, in respect to clinical examination and ECG, in detecting left ventricular (LV) dilatation and systolic dysfunction. METHOD: A group of 100 patients, scheduled for cardiac magnetic resonance imaging (MRI), was prospectively studied. RESULTS: Clinical examination identified moderate-to-severe LV dysfunction, defined as a LV ejection fraction (EF) < 45% at MRI, with a sensitivity of 62% and a specificity of 68%. After ECG, sensitivity and specificity slightly improved (71 and 70%, respectively). After the echocardiographic report, sensitivity reached 84% and specificity 90%. LV EF by echocardiography (routine studies) was closely related with that by MRI (r = 0.84). LV function was scored as undefined in 17% of patients after clinical examination, in 5% of patients after ECG and in no patient after echocardiography (P < 0.0001). Clinical examination identified patients with LV dilatation (LV end-diastolic volume > or = 110 ml/m2) with a poor sensitivity (33%) but a good specificity (88%). After ECG, sensitivity was 39% and specificity 87%; after echocardiography, sensitivity reached 53% and specificity 92%. CONCLUSION: Echocardiography provides information on LV function and dimensions that vastly exceeds that obtained by clinical examination and ECG. This study supports the use of echocardiography to improve patient diagnosis and management after history and physical examination.

Abstract: The paradigm of a shorter pain-to-balloon time decreasing extent of infarct size may be not completely true in transferred patients. This study evaluated the influence of pain-to-balloon time on infarct size as assessed by delayed enhancement magnetic resonance imaging in patients transferred from a peripheral hospital to a tertiary center for primary coronary angioplasty (percutaneous coronary intervention [PCI]). Sixty patients (40 men, 64 +/- 3 years of age) with first acute myocardial infarction were treated within <168, 168 to 222, 223 to 300, and >300 minutes. A presentation score system including clinical, laboratory, and echocardiographic data was used to classify severity of presentation at admission. Magnetic resonance imaging was performed 6 +/- 3 days after PCI. Group 1 had a higher presentation score than did group 2 (p <0.02) and group 3 (p <0.02). Group 1 had a significantly longer delayed enhancement than did group 2 (p <0.002) and group 3 (p <0.03). In conclusion we found that patients with worse presentation are transferred sooner for primary PCI. This approach in these patients does not decrease infarct size likely because of unavoidable delay to reperfusion. This finding suggests a different therapeutic strategy in these patients.

Abstract: OBJECTIVE: We investigated how pathologic Q waves or equivalents predict location, size and transmural extent of myocardial infarction (MI). METHODS: MI characteristics, detected by contrast-enhanced magnetic resonance imaging, were compared with 12-lead electrocardiogram in 79 patients with previous first MI. RESULTS: Q waves involved only the anterior leads (V1-V4) in 13 patients: in all patients MI involved the anterior and anteroseptal walls and apex; 81% of scar tissue was within these regions. Q waves involved only the inferior leads (II, III, aVF) in 13 patients: in 12 of these patients MI involved the inferior and inferoseptal walls; however, only 59% of scar occupied these regions. Q waves involved only lateral leads (V5, V6, I, aVL) in 11 patients: in nine of these patients MI involved the lateral wall but only 27% of scar tissue was within this wall. Q waves involved two electrocardiogram locations in 42 patients. In the 79 patients as a whole, the number of anterior Q waves was related to anterior MI size (r=0.70); however, the number of inferior and lateral Q waves was only weakly related to MI size in corresponding territories (r=0.35 and 0.33). A tall and broad R wave in V1-V2 was a more powerful predictor of lateral MI size than Q waves. Finally, the number of Q waves accurately reflected the transmural extent of the infarction (r=0.70) only in anterior infarctions. CONCLUSION: Q waves reliably predict MI location, size and transmural extent only in patients with anterior infarction. A tall and broad R wave in V1-V2 reflects a lateral MI.

Abstract: BACKGROUND: The effects of subclinical thyroid dysfunction on cardiac outcome are not well defined. METHODS: To assess the relationship between mild thyroid dysfunction and the incidence of death in cardiac patients, we evaluated 3121 cardiac patients. Cardiac and overall deaths were considered. Four groups were defined: euthyroidism, subclinical hypothyroidism (SCH), subclinical hyperthyroidism (SCT), and low triiodothyronine syndrome (low T3). RESULTS: After mean follow-up of 32 months, there were 65 and 140 cardiac and overall deaths (3.4% and 7.3%), respectively, in euthyroidism, 15 and 27 (7.2% and 13.0%) in SCH, 8 and 9 (8.2% and 9.2%) in SCT, and 59 and 119 (6.5% and 13.1%) in low T3. Survival rates for cardiac death were lower in SCH, SCT, and low T3 than in euthyroidism (log-rank test; chi2 = 19.46; P < .001). Survival rates for overall death were lower in SCH and low T3 than in euthyroidism (log-rank test; chi2 = 26.67; P < .001). After adjustment for several risk factors, hazard ratios (HRs) for cardiac death were higher in SCH (HR, 2.40; 95% confidence interval [CI], 1.36-4.21; P = .02), SCT (HR, 2.32; 95% CI, 1.11-4.85; P = .02), and low T(3) (HR, 1.63; 95% CI, 1.14-2.33; P = .007) than in euthyroidism; HRs for overall death were higher in SCH (HR, 2.01; 95% CI, 1.33-3.04; P < .001) and low T3 (HR, 1.57; 95% CI, 1.22-2.01; P < .001) but not in SCT. CONCLUSION: A mildly altered thyroid status is associated with an increased risk of mortality in patients with cardiac disease.

Abstract: A 25 year-old male patient symptomatic for heart palpitations underwent cardiovascular magnetic resonance (CMR) examination. CMR showed ventricular non-compaction cardiomyopathy involving both left and right ventricle. Patient started therapy with beta-blockers with a marked reduction in symptoms. During a three-year follow-up, the patient remained asymptomatic and in a second CMR examination, in 2006, showed no substantial variations in cardiac function.

Abstract: AIMS: The aim of the study was to assess the feasibility and accuracy of an integrated stress imaging algorithm with echo first and second-line Cardiac Magnetic Resonance (CMR) in selected cases. Stress echo (SE) is widely used for non-invasive diagnosis of coronary artery disease (CAD), but difficult patients and ambiguous responses may be met even with top-level technology and expertise. CMR might ideally complement SE in well-selected cases with unfeasible and/or ambiguous and/or submaximal results. METHODS AND RESULTS: 152 in-hospital patients with chest pain and normal baseline function were referred for SE and coronary angiography. Of the initial population, 33 were shunted to CMR due to poor acoustic window or ambiguous or submaximal SE test. The only criterion of positivity for both techniques was the presence of regional wall motion abnormalities in at least 2 contiguous segments. Coronary angiography was performed independently of test results. Significant CAD was identified by a >50% quantitatively assessed diameter reduction in at least 1 major coronary vessel.CAD was present in 88 patients. Interpretable and diagnostic stress test were obtained in 143 patients with the sequential algorithm. The sequential (SE in 110 + CMR in 33 patients) algorithm showed a sensitivity of 76% (95% CI 66% to 85%) specificity of 87% (95% CI 76% to 95%) and accuracy of 80% (95% CI 73% to 86%). CONCLUSION: A sequential functional stress imaging algorithm with stress echo first and stress CMR in selected cases is feasible, clinically realistic and allows an efficient, radiation-free diagnosis of CAD.

Abstract: Increased glucose utilization and regional differences in contractile function are well-known alterations of the failing heart and play an important pathophysiological role. We tested whether, similar to functional derangement, changes in glucose uptake develop following a regional pattern. Heart failure was induced in 13 chronically instrumented minipigs by pacing the left ventricular (LV) free wall at 180 beats/min for 3 wk. Regional changes in contractile function and stress were assessed by magnetic resonance imaging, whereas regional flow and glucose uptake were measured by positron emission tomography utilizing, respectively, the radiotracers [(13)N]ammonia and (18)F-deoxyglucose. In heart failure, LV end-diastolic pressure was 20 +/- 4 mmHg, and ejection fraction was 35 +/- 4% (all P < 0.05 vs. control). Sustained pacing-induced dyssynchronous LV activation caused a more pronounced decrease in LV systolic thickening (7.45 +/- 3.42 vs. 30.62 +/- 8.73%, P < 0.05) and circumferential shortening (-4.62 +/- 1.0 vs. -7.33 +/- 1.2%, P < 0.05) in the anterior/anterior-lateral region (pacing site) compared with the inferoseptal region (opposite site). Conversely, flow was reduced significantly by approximately 32% compared with control and was lower in the opposite site region. Despite these nonhomogeneous alterations, regional end-systolic wall stress was uniformly increased by 60% in the failing LV. Similar to wall stress, glucose uptake markedly increased vs. control (0.24 +/- 0.004 vs. 0.07 +/- 0.01 micromol x min(-1) x g(-1), P < 0.05), with no significant regional differences. In conclusion, high-frequency pacing of the LV free wall causes a dyssynchronous pattern of contraction that leads to progressive cardiac failure with a marked mismatch between increased glucose uptake and regional contractile dysfunction.

Abstract: OBJECTIVE: Obese subjects have a risk of death from cardiovascular disease higher than those with normal body weight. Obese patients, however, have a better outcome when undergoing coronary revascularisation, and when suffering from heart failure or chronic kidney disease. The term 'obesity paradox' underlines the divergence between increased risk and better outcome in sick obese patients. We tested the hypothesis that the obesity paradox could also occur in myocardial infarction. METHODS: A group of 89 patients (mean age 62 +/- 11 years) with previous myocardial infarction (Q-wave in 72 patients) underwent contrast-enhanced MRI. RESULTS: Areas of delayed contrast enhancement (which reflects myocardial necrosis) were present in 15 +/- 9% of left ventricular myocardium. Infarct size was not influenced by patient age, gender, history of arterial hypertension, hypercholesterolaemia, hypertriglyceridaemia nor tobacco smoking. Infarct size, however, was larger in insulin-dependent diabetic patients (P = 0.06) and in those with a family history of premature coronary artery disease (P = 0.06). Surprisingly, infarct size was smaller in obese patients (11 +/- 4% of left ventricular myocardium) than in those with normal body weight (16 +/- 9% of left ventricular myocardium, P = 0.03). Insulin-dependent diabetes mellitus, obesity and family history of coronary artery disease were the only independent predictors of infarct size at multiple linear regression analysis. CONCLUSIONS: Owing to its limitations (small sample size and exclusion of extremely obese patients), this study generates a working hypothesis, which should be tested in larger prospective studies, that the obesity paradox could also occur in myocardial infarction.