Diffusion-weighted imaging in hypertrophic cardiomyopathy: association with high T2-weighted signal intensity in addition to late gadolinium enhancement.

Diffusion-weighted imaging (DWI) has been confirmed to be associated with late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM). In this context, we aimed to study whether DWI could reflect the active tissue injury and edema information of HCM which were usually indicated by T2 weighted images. Forty HCM patients were examined using a 3.0 T magnetic resonance scanner. Cine, T2-weighted short tau inversion recovery (T2-STIR), DWI and LGE sequences were acquired. T1 mapping was also included to quantify the focal and diffuse fibrosis. Cardiac troponin I (cTnI) was tested to assess the recently myocardial injury. Student's t-test, Mann-Whitney U test, One-way analysis, Kruskal-Wallis analysis, the Spearman correlation analysis, and multivariable regression were used in this study. The apparent diffusion coefficient (ADC) was significantly elevated in the cTnI positive group (P = 0.01) and correlated with LGE (ρ = 0.312, P = 0.049) and HighT2 extent (ρ = 0.443, P = 0.004) in the global level. In the segmental analysis, the ADC significantly differentiated the segments with and without HighT2/LGE presence (P = 0.00). The average ADC values were higher in segments with HighT2 and LGE coexistence than in those with only LGE presence (P < 0.05). Multivariable regression indicated that segmental HighT2 and LGE were both contributing factors to the ADC values. In this study of HCM, we confirmed that ADC as a molecular diffusion parameter reflects the replacement fibrosis of myocardium. Moreover, it also reveals edema extent and its association with serum cTnI.

Acute impact of an endurance race on cardiac function and biomarkers of myocardial injury in triathletes with and without myocardial fibrosis.

AIMS: The aim of this study was to investigate the occurrence of myocardial injury and cardiac dysfunction after an endurance race by biomarkers and cardiac magnetic resonance in triathletes with and without myocardial fibrosis. METHODS AND RESULTS: Thirty asymptomatic male triathletes (45 ± 10 years) with over 10 training hours per week and 55 ± 8 ml/kg per minute maximal oxygen uptake during exercise testing were studied before (baseline) and 2.4 ± 1.1 hours post-race. Baseline cardiac magnetic resonance included cine, T1/T2, late gadolinium enhancement (LGE) and extracellular volume imaging. Post-race non-contrast cardiac magnetic resonance included cine and T1/T2 mapping. Non-ischaemic myocardial fibrosis was present in 10 triathletes (LGE+) whereas 20 had no fibrosis (LGE-). At baseline, LGE + triathletes had higher peak exercise systolic blood pressure with 222 ± 21 mmHg compared to LGE- triathletes (192 ± 30 mmHg, P < 0.01). Post-race troponin T and creatine kinase MB were similarly increased in both groups, but there was no change in T2 and T1 from baseline to post-race with 54 ± 3 ms versus 53 ± 3 ms (P = 0.797) and 989 ± 21 ms versus 989 ± 28 ms (P = 0.926), respectively. However, post-race left atrial ejection fraction was significantly lower in LGE + triathletes compared to LGE- triathletes (53 ± 6% vs. 59 ± 6%, P < 0.05). Furthermore, baseline atrial peak filling rates were lower in LGE - triathletes (121 ± 30 ml/s/m2) compared to LGE + triathletes (161 ± 34 ml/s/m2, P < 0.01). Post-race atrial peak filling rates increased in LGE- triathletes to 163 ± 46 ml/s/m2, P < 0.001), but not in LGE + triathletes (169 ± 50ml/s/m2, P = 0.747). CONCLUSION: Despite post-race troponin T release, we did not find detectable myocardial oedema by cardiac magnetic resonance. However, the unfavourable blood pressure response during exercise testing seemed to be associated with post-race cardiac dysfunction, which could explain the occurrence of myocardial fibrosis in triathletes.

Synthetic hematocrit derived from the longitudinal relaxation of blood can lead to clinically significant errors in measurement of extracellular volume fraction in pediatric and young adult patients.

BACKGROUND: Extracellular volume fraction (ECV) is altered in pathological cardiac remodeling and predicts death and arrhythmia. ECV can be quantified using cardiovascular magnetic resonance (CMR) T1 mapping but calculation requires a measured hematocrit (Hct). The longitudinal relaxation of blood has been used in adults to generate a synthetic Hct (estimate of true Hct) but has not been validated in pediatric populations. METHODS: One hundred fourteen children and young adults underwent a total of 163 CMRs with T1 mapping. The majority of subjects had a measured Hct the same day (N = 146). Native and post-contrast T1 were determined in blood pool, septum, and free wall of mid-LV, avoiding areas of late gadolinium enhancement. Synthetic Hct and ECV were calculated and intraclass correlation coefficient (ICC) and linear regression were used to compare measured and synthetic values. RESULTS: The mean age was 16.4 ± 6.4 years and mean left ventricular ejection fraction was 59% ± 9%. The mean measured Hct was 41.8 ± 3.0% compared to the mean synthetic Hct of 43.2% ± 2.9% (p < 0.001, ICC 0.46 [0.27, 0.52]) with the previously published model and 41.8% ± 1.4% (p < 0.001, ICC 0.28 [0.13, 0. 42]) with the locally-derived model. Mean measured mid-free wall ECV was 30.5% ± 4.8% and mean synthetic mid-free wall ECV of local model was 29.7% ± 4.6% (p < 0.001, ICC 0.93 [0.91, 0.95]). Correlations were not affected by heart rate and did not significantly differ in subpopulation analysis. While the ICC was strong, differences between measured and synthetic ECV ranged from -8.4% to 4.3% in the septum and -12.6% to 15.8% in the free wall. Using our laboratory's normal cut-off of 28.5%, 59 patients (37%) were miscategorized (53 false negatives, 6 false positives) with published model ECV. The local model had 37 miscategorizations (20 false negatives, 17 false positives), significantly fewer but still a substantial number (23%). CONCLUSIONS: Our data suggest that use of synthetic Hct for the calculation of ECV results in miscategorization of individual patients. This difference may be less significant once synthetic ECV is calculated and averaged over a large research cohort, making it potentially useful as a research tool. However, we recommend formal measurement of Hct in children and young adults for clinical CMRs.

Noninvasive Bioelectrical Impedance for Predicting Clinical Outcomes in Outpatients With Heart Failure.

BACKGROUND: Noninvasive bioelectrical impedance analysis (BIA) has shown promise in acute heart failure (HF) management. To our knowledge, its use in predicting outcomes in outpatients with chronic HF patients has not been well described. METHODS AND RESULTS: BIA assessment of edema index was performed in 359 outpatients with HF using the InBody 520 scale. Edema index was calculated by dividing extracellular by total body water. Patients were stratified into those with low (≤0.39) and high (>0.39) edema indices. The outcome of interest was death, urgent transplant, or ventricular assist device over 2-year follow up. Patients with a high edema index were older, had higher B-type natriuretic peptide values and New York Heart Association Class. Patients with a high edema index had poorer outcomes (unadjusted hazard ratio 1.90, 95% confidence intervals 1.05-3.56). However, in multivariate analyses, a high edema index was not an independent predictor of outcomes (adjusted hazard ratio 1.21, 95% confidence interval 0.51-2.90). CONCLUSIONS: A high edema index using a bioimpedance scale in a HF clinic correlated with patient outcomes in unadjusted analyses, but was not a predictor of outcomes once other measures of HF severity are accounted for. As a noninvasive measure of volume status, use of BIA in a HF clinic may be beneficial in determining patient prognosis and treatment when other outcome predictors are not immediately available.

Pedal Edema as an Indicator of Early Heart Failure in the Community: Prevalence and Associations With Cardiac Structure/Function and Natriuretic Peptides (MESA [Multiethnic Study of Atherosclerosis]).

BACKGROUND: The prevalence of pedal edema (PE) and its associations with abnormal cardiac structure/function, natriuretic peptides, and incident heart failure (HF) is unknown, especially in community-dwelling adults without a history of cardiovascular disease. METHODS AND RESULTS: Out of 5004 MESA (Multiethnic Study of Atherosclerosis) participants who had cardiac magnetic resonance imaging, 4196 had complete data and were included in this analysis (3501 for the right ventricle analysis). Logistic regression and Cox proportional hazard analyses were used to assess the associations among self-reported PE, 2-pillow orthopnea, paroxysmal nocturnal dyspnea, left and right ventricular structure and function, natriuretic peptide levels, and incident HF. PE was present in 28% of the participants. PE was not associated with overt left or right ventricular systolic dysfunction (ejection fraction <50%). PE was associated with 2-pillow orthopnea (odds ratio 1.66; 95% confidence interval [CI], 1.30-2.12), paroxysmal nocturnal dyspnea (odds ratio 1.95; 95% CI, 1.55-2.44), and abnormal N-terminal pro-B-type natriuretic peptide levels (defined as >400 pg/mL; odds ratio 1.80; 95% CI, 1.21-2.68) in adjusted models. After a mean of 10.2 years of follow-up, 184/4196 (4.4%) participants had an adjudicated incident HF hospitalization. PE was associated with incident HF hospitalization in models adjusted for age, sex, and race (hazard ratio 1.44; 95% CI, 1.05-1.97). This association persisted after adding additional covariates, including comorbidities, baseline left ventricular ejection fraction, and antecedent myocardial infarction (hazard ratio 1.43; 95% CI, 1.02-1.99). The association of PE with incident HF was attenuated by further adjustment for N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: PE is prevalent in community-dwelling adults without clinically recognized cardiovascular disease and associated with future hospitalized HF.

Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: This study aimed to determine whether remote ischemic conditioning (RIC) initiated prior to primary percutaneous coronary intervention (PPCI) could reduce myocardial infarct (MI) size in patients presenting with ST-segment elevation myocardial infarction. BACKGROUND: RIC, using transient limb ischemia and reperfusion, can protect the heart against acute ischemia-reperfusion injury. Whether RIC can reduce MI size, assessed by cardiac magnetic resonance (CMR), is unknown. METHODS: We randomly assigned 197 ST-segment elevation myocardial infarction patients with TIMI (Thrombolysis In Myocardial Infarction) flow grade 0 to receive RIC (four 5-min cycles of upper arm cuff inflation/deflation) or control (uninflated cuff placed on upper arm for 40 min) protocols prior to PPCI. The primary study endpoint was MI size, measured by CMR in 83 subjects on days 3 to 6 after admission. RESULTS: RIC reduced MI size by 27%, when compared with the MI size of control subjects (18.0 ± 10% [n = 40] vs. 24.5 ± 12.0% [n = 43]; p = 0.009). At 24 h, high-sensitivity troponin T was lower with RIC (2,296 ± 263 ng/l [n = 89] vs. 2,736 ± 325 ng/l [n = 84]; p = 0.037). RIC also reduced the extent of myocardial edema measured by T2-mapping CMR (28.5 ± 9.0% vs. 35.1 ± 10.0%; p = 0.003) and lowered mean T2 values (68.7 ± 5.8 ms vs. 73.1 ± 6.1 ms; p = 0.001), precluding the use of CMR edema imaging to correctly estimate the area at risk. Using CMR-independent coronary angiography jeopardy scores to estimate the area at risk, RIC, when compared with the control protocol, was found to significantly improve the myocardial salvage index (0.42 ± 0.29 vs. 0.28 ± 0.29; p = 0.03). CONCLUSIONS: This randomized study demonstrated that in ST-segment elevation myocardial infarction patients treated by PPCI, RIC, initiated prior to PPCI, reduced MI size, increased myocardial salvage, and reduced myocardial edema.

Diagnostic and prognostic value of osteopontin in patients with acute congestive heart failure.

AIMS: To evaluate the diagnostic and prognostic value of osteopontin in patients with acute dyspnoea and/or peripheral oedema suspected of having acute congestive heart failure (aCHF). METHODS AND RESULTS: A total of 401 patients presenting with acute dyspnoea and/or peripheral oedema to the emergency department were prospectively enrolled and followed up for up to 5 years. Blood samples for biomarker measurements were collected on admission to the emergency department. Osteopontin combined with NT-proBNP vs. NT-proBNP alone for diagnosis of aCHF was tested. Additionally, osteopontin vs. NT-proBNP for prognostic outcomes (i.e. all-cause mortality, aCHF-related rehospitalization, and both in combination) was tested. The diagnostic and prognostic capacity of osteopontin was tested by C-statistics, reclassification indices, and multivariable Cox prediction models. Osteopontin plus NT-proBNP improved the diagnostic capacity for aCHF diagnosis [accuracy 76%, 95% confidence interval (CI) 72-80%; specificity 74%, 95% CI 69-79%, net reclassification improvement (NRI) +0.10] compared with NT-proBNP alone in the emergency department (P = 0.0001). Osteopontin independently predicted all-cause mortality and aCHF-related rehospitalization after 1 and 5 years. Compared with NT-proBNP, osteopontin was of superior prognostic value, specifically in aCHF patients and for the prognostic outcome of aCHF-related rehospitalization. CONCLUSION: Osteopontin improves aCHF diagnosis when combined with NT-proBNP. Osteopontin identifies aCHF patients with high 1- and 5-year mortality and rehospitalization risk, and adds prognostic value to NT-proBNP. Trial registration NCT00143793.

Diagnosis of viral myocarditis by cardiac magnetic resonance and viral genome detection in peripheral blood.

In patients with acute myocarditis, viral genome can be detected in plasma and peripheral leukocytes. Its relationship with active myocardial inflammation, however, is not well understood. Myocardial edema as a feature of inflammation and myocardial necrosis or fibrosis can be frequently observed in patients with acute myocarditis by cardiovascular magnetic resonance (CMR). We assessed the association of viral genome presence in peripheral blood samples with myocardial edema and irreversible injury. We examined consecutive patients with clinically suspected myocarditis after an episode of viral illness. State-of-the-art methods were used for detecting myocardial edema and irreversible injury using CMR and viral genome applying reverse transcribed, nested polymerase chain reaction in peripheral blood samples. The specificity of viral amplification products was confirmed by automatic DNA sequencing. Of a total of 55 patients (53.5 ± 15.6 years), 21 were positive for viral genome in peripheral leukocytes. Interestingly, 18 (86%) of these patients also showed global myocardial edema, as compared to only 7/34 (21%) without PCR evidence for viral genome. The overall agreement between CMR criteria for edema and viral PCR was 84%. In contrast, there was no significant relationship of viral genome presence with myocardial necrosis or scars. In patients with clinically suspected myocarditis, myocardial edema but not irreversible myocardial injury is associated with the presence of viral genome in peripheral blood.

Detecting myocardial ischemia at rest with cardiac phase-resolved blood oxygen level-dependent cardiovascular magnetic resonance.

BACKGROUND: Fast noninvasive identification of ischemic territories at rest (before tissue-specific changes) and assessment of functional status can be valuable in the management of severe coronary artery disease. This study investigated the use of cardiac phase-resolved blood oxygen level-dependent (CP-BOLD) cardiovascular magnetic resonance in detecting myocardial ischemia at rest secondary to severe coronary artery stenosis. METHODS AND RESULTS: CP-BOLD, standard cine, and T2-weighted images were acquired in canines (n=11) at baseline and within 20 minutes of ischemia induction (severe left anterior descending stenosis) at rest. After 3 hours of ischemia, left anterior descending stenosis was removed, and T2-weighted and late-gadolinium-enhancement images were acquired. From standard cine and CP-BOLD images, end-systolic and end-diastolic myocardium was segmented. Affected and remote sections of the myocardium were identified from postreperfusion late-gadolinium-enhancement images. Systolic-to-diastolic ratio (S/D), quotient of mean end-systolic and end-diastolic signal intensities (on CP-BOLD and standard cine), was computed for affected and remote segments at baseline and ischemia. Ejection fraction and segmental wall thickening were derived from CP-BOLD images at baseline and ischemia. On CP-BOLD images, S/D was >1 (remote and affected territories) at baseline; S/D was diminished only in affected territories during ischemia, and the findings were statistically significant (ANOVA, post hoc P<0.01). The dependence of S/D on ischemia was not observed in standard cine images. Computer simulations confirmed the experimental findings. Receiver-operating characteristic analysis showed that S/D identifies affected regions with performance (area under the curve, 0.87) similar to ejection fraction (area under the curve, 0.89) and segmental wall thickening (area under the curve, 0.75). CONCLUSIONS: Preclinical studies and computer simulations showed that CP-BOLD cardiovascular magnetic resonance could be useful in detecting myocardial ischemia at rest. Patient studies are needed for clinical translation.

Edema index established by a segmental multifrequency bioelectrical impedance analysis provides prognostic value in acute heart failure.

OBJECTIVES: A segmental multifrequency bioelectrical impedance analysis (SMBIA) is a noninvasive and reproducible modality for estimating the fluid state. The aim of this study was to test whether the SMBIA-derived edema index provides prognostic value in patients hospitalized due to acute heart failure (AHF). METHODS: To estimate the 6-month prognostic value of the predischarge edema index in patients hospitalized due to AHF, 112 patients were consecutively enrolled. Both predischarge edema index and B-type natriuretic peptide (BNP) were measured. Outcome follow-up focused on heart failure-related and all-cause re-hospitalizations and all events. RESULTS: On the basis of a cutoff value of edema index of 0.390, patients were separated into two groups: edema index more than 0.390 (n = 44) and edema index of 0.390 or less (n = 68). Compared with patients with edema index 0.390 or less, those with edema index of more than 0.390 were older, had lower blood albumin and hemoglobin levels, and had higher predischarge BNP levels, functional class, incidence of diabetes mellitus, valvular cause, and diuretic use. Although edema indexes were correlated with BNP levels (r = 0.47, P < 0.0001), a mismatch was noted in 33 (29%) patients. Univariate and multivariate analysis showed that an edema index of more than 0.390 predicted a higher incidence of heart failure-related re-hospitalization [odds ratio (OR) = 4.14, confidence interval (CI) = 1.05-15.28, P = 0.04] and all events (OR = 3.97, CI = 1.4-11.25, P = 0.01). The edema index provided a prognostic value superior to that of BNP. Reducing the edema index in high-risk patients resulted in fewer heart failure-related re-hospitalizations (OR = 0.81, CI = 0.77-0.84, P < 0.001) and all events (OR = 0.8, CI = 0.76-0.85, P < 0.001). CONCLUSION: Edema index provides 6-month prognostic values in patients hospitalized due to AHF. Reducing the edema index in high-risk patients results in better outcomes.

Effects of tolvaptan on volume overload in Japanese patients with heart failure: results of a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

PURPOSE: Tolvaptan may reduce the signs of volume overload in heart failure (HF) patients who experience volume overload despite using conventional diuretics. In this study, we evaluated the dose-response effects of tolvaptan on weight loss, urine volume and electrolyte excretion in furosemide-treated Japanese HF patients exhibiting volume overload. METHODS: In the study, 117 HF patients with volume overload on stable doses of furosemide (≥ 40 mg/day) were treated with tolvaptan (15, 30 or 45 mg) or placebo once-daily for 7 days. RESULTS: The decrease in body weight from baseline to the day after the final dose with 15, 30 or 45 mg tolvaptan (-1.62 ± 1.55, -1.35 ± 1.54 and -1.85 ± 1.10 kg, respectively), was significantly greater compared with that in the placebo group (-0.53 ± 0.96 kg) (p < 0.05). However, the decrease in body weight with tolvaptan was not significantly dose-dependent. Signs of volume overload improved at all doses of tolvaptan. Tolvaptan elicited a dose-dependent increase in urine volume and a decrease in urine osmolality, but did not affect urinary sodium or potassium excretion. Adverse reactions associated with diuresis were most frequently observed at the higher doses of tolvaptan. CONCLUSIONS: Once-daily tolvaptan (15, 30 or 45 mg) was effective and tolerable as an add-on treatment to furosemide therapy in Japanese HF patients with volume overload.

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PURPOSE: Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. METHODS: A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. RESULTS: Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. CONCLUSION: Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study.

PURPOSE: Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload. METHODS: Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters. RESULTS: Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days. CONCLUSIONS: This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.

Phase III clinical pharmacology study of tolvaptan.

PURPOSE: This study aimed to investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of tolvaptan, an orally effective vasopressin V2-receptor antagonist. METHODS: This was a multicenter, randomized, double-blind, parallel group study. Tolvaptan was administered at 7.5 or 15 mg, in combination with furosemide, for 7 days in Japanese heart failure (HF) patients with volume overload that had not resolved despite receiving furosemide. RESULTS: The blood concentration of tolvaptan was maintained at a higher concentration for a longer time in patients who received 15 mg/day when compared with patients who received 7.5 mg/day. Tolvaptan increased urine volume and increased weight loss dose-dependently when used in combination with furosemide. Importantly, tolvaptan enhanced water diuresis without affecting blood electrolyte levels. CONCLUSION: Tolvaptan exerts diuretic effects and causes body weight loss at the low dose of 7.5 mg; however, these effects were less than those elicited by 15 mg tolvaptan.

Association of NT-proBNP with severity of heart valve disease in a medical patient population presenting with acute dyspnea or peripheral edema.

BACKGROUND AND AIM OF THE STUDY: The study aim was to perform a comprehensive evaluation of the association between N-terminal pro B-type natriuretic peptide (NT-proBNP) and the severity of heart valve diseases in a typical clinical population presenting with acute dyspnea or peripheral edema. METHODS: Among 401 eligible patients, 210 demonstrated evaluable complete echocardiographic examinations. Plasma levels of NT-proBNP were measured after the initial clinical evaluation. RESULTS: Patients with a prior valve replacement had higher plasma levels of NT-proBNP (median 3,366 pg/ml; n = 10) compared to all other patients (median 931 pg/ml; n = 200) (p < 0.05). In univariable analyses, NT-proBNP levels correlated with multiple valve diseases (r = 0.5; p < 0.001) and the severities of specific heart valve diseases, including aortic valve stenosis (AS) and regurgitation (AR), tricuspid (TR) and mitral valve regurgitation (MR) (p < 0.001). Within multivariable linear regression models, multiple heart valve diseases (Beta = 0.21; T = 3.56; p = 0.0001) and specifically valve regurgitations (AR (Beta = 0.16; T = 2.54; p = 0.012), MR (Beta = 0.36; T = 5.55; p = 0.0001), TR (Beta = 0.17; T = 2.55; p = 0.012)) were associated with increasing plasma levels of NT-proBNP. Patients with NT-proBNP plasma levels > 1,100 pg/ml showed the highest risk for future clinical events (odds ratio (OR) 4.86; p = 0.02), followed by patients with TR (OR 3.17; p = 0.03) and AS (OR 3.49; p = 0.06). CONCLUSION: In addition to clinical assessment and echocardiographic evaluation, the measurement of plasma NT-proBNP levels may serve as a valuable additional indicator of the severity of heart valve disease in individual patients.

Nesiritide following maze and mitral valve surgery.

BACKGROUND: Fluid retention following "maze" and mitral valve surgery has been associated with diminished levels of atrial natriuretic peptide (ANP). We hypothesized prophylactic administration of nesiritide (human recombinant brain natriuretic peptide, NES, Natrecor, Scios, Fremont, CA, USA), which has similar physiologic properties to ANP and would promote diuresis in maze and mitral patients postoperatively. METHODS: Randomized, blinded, prospective pilot study comparing patients undergoing maze and mitral surgery including excision of the left atrial appendage. Three hours after cardiopulmonary bypass, patients received either a 72-hour infusion of NES at 0.01 mcg/kg/min (n = 9) or placebo (n = 10). Diuresis, diuretics, time to extubation, oxygenation, ANP, and serum Endothelin-1 levels were measured. Nonparametric analysis with Mann-Whitney test was performed with SPSS (SPSS Inc., Chicago, IL, USA). RESULTS: In both groups, postoperative ANP levels fell from baseline (NES 330 to 280 ng/mL and control 220 to 150 ng/mL). There were no significant differences in patients receiving NES compared to controls in diuresis (1.33 mL/kg/hour urine output NES vs. 1.68 mL/kg/hour controls, p = 0.14); furosemide dosage (0.04 mg/kg/hour NES vs. 0.04 mg/kg/hour controls, p = 0.08); time to extubation (17.5 hours NES vs. 19.5 control, p = 0.42) or PaO2/FiO2 ratio at 48 hours (NES 200 vs. 273 control, p > 0.05). Endothelin-1 levels were higher at baseline with NES but not at 1 and 72 hours after cardiopulmonary bypass (NES 3.1, 3.8, 2.9 pg/mL vs. control 1.85, 4.05, 2.75 pg/mL; p = 0.01, 0.77, 0.47). CONCLUSIONS: This pilot study did not demonstrate additional diuresis with nesiritide in postoperative mitral/maze patients already following a loop diuretic protocol.

Current approaches to monitoring and management of heart failure.

Decompensation in patients with congestive heart failure remains a treatment problem. Earlier detection of decompensation may result in a lessened need for hospitalization and perhaps an interruption of the as-yet-undetermined processes during decompensation that lead to an adverse effect on the natural history of heart failure. B-type natriuretic peptide is produced by right and/or left ventricular tissue in response to an increase in ventricular wall stress and may be used as an indicator of decompensation. New directions in monitoring now include novel device-based algorithms that determine either intraventricular pressure or intrathoracic impedance. When combined with clinical assessment, weight monitoring, and symptom assessment, these newer monitoring platforms may yield improvements in the natural history of heart failure.

Circulating levels of tumor necrosis factor-alpha correlate positively with severity of peripheral oedema in patients with right heart failure.

BACKGROUND: Several previous studies have shown that circulating levels of tumor necrosis factor-alpha (TNF) are elevated in patients with advanced congestive heart failure. However, the relationship between circulating levels of TNF and severity of peripheral oedema in these patients has not been previously evaluated. AIMS: To investigate the relationship between circulating levels of TNF, and severity of peripheral oedema in patients with right-sided heart failure (RHF). METHODS AND RESULTS: Circulating levels of TNF were measured in 15 healthy volunteers, and in 83 patients with RHF with various levels of peripheral oedema. At presentation, 13 patients had no peripheral oedema (grade 0), 22 patients had mild peripheral oedema (grade 1), 23 patients had moderate peripheral oedema (grade 2), and 25 patients had severe peripheral oedema (grade 3). The values of circulating TNF levels (mean +/- S.E.M.) at presentation in the control group and in the RHF patients (oedema grades 0-3) were 2.98+/-0.21, 4.22+/-0.55, 4.67+/-0.29, 7.66+/-0.44, and 10.94+/-0.67 pg/mL respectively. There was a significant difference between the groups (p < 0.0001, ANOVA), and a significant positive correlation was found between circulating TNF levels and severity of peripheral oedema (r = 0.77, p<0.0001). CONCLUSION: A significant relationship is present between circulating levels of TNF and severity of peripheral oedema in patients with RHF.

Passive infusion: a simple delivery method for retrograde cardioplegia.

Some damage to the capillaries and increase in myocardial edema have been shown when retrograde cardioplegia perfusion pressure exceeds 40-50 mmHg, or possibly when it falls within this pressure interval. To avoid these complications, we designed a very simple delivery method for retrograde cardioplegia: passive continuous infusion by gravitational force alone. From August 2002 through April 2003, 147 patients undergoing elective coronary artery bypass surgery were randomly allocated into 2 groups. In both groups, isothermic blood cardioplegic solution was infused continuously in a retrograde fashion, after antegrade cardioplegic arrest. Group 1 (n=76) received retrograde infusion passively by gravitational force, while Group 2 (n=71) received retrograde infusion from a manually controlled pressure bag, with the pressure maintained at about 40 mmHg. Myocardial biopsy specimens were taken just before the aorta was declamped, and myocardial edema was scored upon histopathologic examination. Postoperative myocardial damage was evaluated with periodic measurements of CK-MB isoenzyme and cardiac troponin T levels. We recorded cardioplegic infusion pressures and rates, and the total amount of potassium administered. The mean cardioplegic infusion pressures and rates, total potassium levels, and cardioplegic solution amounts were significantly lower in Group 1 than Group 2. Histologic observations revealed significantly less myocardial edema in Group 1. There were no differences between groups in CK-MB isoenzyme or cardiac troponin T levels, mortality, or morbidity. Retrograde continuous infusion of isothermic blood cardioplegic solution by gravitational force alone appears to provide satisfactory myocardial protection and to eliminate the harmful effects of higher pressures upon the myocardium.