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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Objective Our aim was to investigate the impact of the sodium glucose cotransporter type 2 (SGLT2) inhibitor on the left ventricular (LV) diastolic function in type 2 diabetes mellitus (T2DM) patients with chronic heart failure (HF) complicating cardiovascular risk factors. Methods We analyzed data from our previous prospective multicenter study, in which we investigated the effect of dapagliflozin on the LV diastolic function of T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least 1 antidiabetic drug other than SGLT2 inhibitors started treatment with dapagliflozin. Echocardiography was performed at baseline and six months after the administration of dapagliflozin. Cardiovascular risk factors other than T2DM were age, gender, hypertension, dyslipidemia, history of cardiovascular events and overweight. Results The LV diastolic function, defined as the ratio of the mitral inflow E to the mitral e' annular velocities (E/e'), significantly decreased from 9.3 to 8.5 by six months after the administration of dapagliflozin (p=0.020) as previously reported. A multivariate logistic regression analysis showed that dyslipidemia was the only independent determinant of improvement in the E/e' after the administration of dapagliflozin among cardiovascular risk factors. Furthermore, the relative change in the E/e' from baseline to six months after the administration of dapagliflozin for HF patients with preserved ejection fraction (HFpEF) and dyslipidemia was significantly larger than that for HFpEF patients without dyslipidemia (-15.2% vs. 29.6%, p=0.014), but no such finding was observed in non-HFpEF patients. Conclusion SGLT2 inhibitors may exert a more beneficial effect on the LV diastolic function for T2DM patients with stable HF, especially those with complicating dyslipidemia, than existing treatments.

This study aims to test the hypothesis that the effect of excimer laser coronary angioplasty (ELCA) not only vaporizes thrombi and their underlying coronary plaque, it also changes their quality. We performed a series of cross-sectional analyses in 52 lesions in 51 patients before and after ELCA with integrated backscatter-intravascular ultrasound (IB-IVUS). The constituent parts of the plaque can be assessed by IB-IVUS (i.e., calcified, fibrous, lipid) according to integrated backscatter values. Minimum lumen diameter, lumen volume and vessel volume expanded after ELCA, while plaque volume did not significantly decrease. There was also a decrease of ‘lipid’ component (35.4–30.3%, P P

Funding Acknowledgements Type of funding sources: None. Background Type 2 diabetes mellitus (T2DM) is a well-known risk factor for heart failure (HF), even in patients without a structural heart disease or a symptom of HF. Diabetes-related cardiomyopathy is presented as an left ventricular (LV) diastolic dysfunction, which, like cardiovascular disease, is a contributor of the development of HF in both patients with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Furthermore, comorbid factors other than T2DM also have been identified as high risk factors for of progression to HF. Dapagliflozin is a sodium glucose cotransporter type 2 (SGLT2) inhibitor, and represents a new class of anti-hyperglycemic agents for T2DM. A result from a recent large clinical trial showed that dapagliflozin reduced risk of worsening HF or death from cardiovascular causes for patients with HFrEF compared to those who received a placebo, regardless of the presence or absence of T2DM. However, the effect of SGLT2 inhibitors on LV diastolic function in T2DM patients with HF who had cardiovascular risk factors other than T2DM remains uncertain. Purpose Our purpose was to investigate the impact of dapagliflozin on LV diastolic function in T2DM patients with stable HF complicating cardiovascular risk factors. Methods We analyzed data from our previous prospective multicenter study, which investigate the effect of dapagliflozin on LV diastolic function of 53 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitor started the administration of dapagliflozin. Cardiovascular risk factors other than T2DM was determined as age, gender, hypertension, dyslipidemia, history of cardiovascular events and overweight. Results E/e′ significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p = 0.020) as previously described. Multivariate logistic regression analysis showed that dyslipidemia was the only independent determinant of an improvement of E/e’ among cardiovascular risk factors. Furthermore, relative changes in E/e’ from baseline to 6 months after administration of dapagliflozin seen in HFpEF patients with dyslipidemia were significantly larger than those in HFpEF patients without dyslipidemia (-15.2% vs. 29.6%, p = 0.014), but such a difference was not observed in non-HFpEF patients. In addition, relative changes in high-density lipoprotein cholesterol (HDL-C) from baseline to 6 months after administration of dapagliflozin had significant correlation with those in E/e’ (r=-0.300, p = 0.038). However, such correlations were not observed in low-density lipoprotein cholesterol (LDL-C) and triglyceride (r = 0.05, p = 0.72 and r = 0.05, p = 0.73). Conclusion: Dapagliflozin was more beneficial effect on LV diastolic function for T2DM patients with stable HF, especially those with complicating dyslipidemia. Our findings may thus offer a new insight into the management of T2DM patients with HF. Abstract Figure.

Cardiac angiosarcoma is a rare malignant neoplasm, the gold standard treatment is surgical resection. Our patient, an 81-year old Japanese woman, was admitted to hospital after chest pain over a month-long period. Transthoracic echocardiography (TTE) showed a heterogeneous and irregular mass-like lesion measuring approximately 45 mm and arising from the right ventricular free wall. Transesophageal echocardiography showed the lesion had a mobile portion. Considering the possibility of malignancy and a high risk of embolism and obstruction, we performed surgical resection of the tumour. Histological and immunohistochemical findings led to diagnosis of cardiac angiosarcoma. One year after surgery, TTE and CT showed no evidence of recurrence of angiosarcoma.

Background Type 2 diabetes mellitus (T2DM) has come to be considered an independent predictor of mortality, and also a contributor to the development of heart failure (HF) with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Left ventricular (LV) longitudinal myocardial dysfunction as assessed in terms of lower global longitudinal strain (GLS), has been identified even in T2DM patients with preserved LV ejection fraction (LVEF), and should be considered the first marker of a preclinical form of DM-related cardiac dysfunction, leading to HFpEF. Sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a new class of anti-hyperglycemic agents for T2DM, but the effect of SGLT2 inhibitors on LV longitudinal myocardial function in T2DM patients with HF remains uncertain. To examine this effect, as well as the association of LV longitudinal myocardial function with LV diastolic function after administration of SGLT2 inhibitor in T2DM patients with stable HF, we analyzed data from our previous prospective multicenter study, in which we investigated the effect of SGLT2 inhibitor on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Methods Our previous trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e' annular velocities (E/e'). LV longitudinal myocardial function was assessed as GLS based on the current guidelines. Results E/e' significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p=0.020) as previously described, while GLS showed significant improvement from 15.5±3.5% to 16.9±4.1% (p Conclusion Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF. Representative case Funding Acknowledgement Type of funding source: None

Background The objective of this study was to investigate the impact of sodium glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV) diastolic function of type 2 diabetes mellitus (T2DM) patients with heart failure (HF). Methods This trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin. The physical examinations, blood tests, and echocardiography were performed at baseline and 6 months after administration of dapagliflozin. The primary endpoint was defined as a change in mitral inflow E and mitral e′ annular velocities (E/e′) between baseline and 6 months after the administration of dapagliflozin. The secondary end points consisted of a change in brain natriuretic peptide (BNP), LV mass index (LVMI) and left atrial volume index (LAVI). Results E/e′ significantly decreased from 9.3 to 8.5 cm/s (p = 0.020) 6 months after administration of dapagliflozin. LAVI and LVMI significantly decreased from 31 to 26 mL/m2 (p = 0.001), and from 75.0 to 67.0 g/m2 (p Conclusion This prospective multicenter trial showed the beneficial effect of SGLT2 inhibitors on LV diastolic functional parameters for T2DM patients with HF. Our findings may thus offer a new insight into the management of T2DM patients. Trial registration UMIN000019789, Registered 28 September 2014, Date of registration: 11/14/2015, Date of enrolment of the first participant to the trial: 6/15/2016, Date of enrolment of the last participant to the trial: 12/9/2017

Background Human atrial natriuretic peptide (hANP) and spontaneous nitric oxide (NO) donor share cyclic guanosine monophosphate (cGMP) as a second messenger, but their effect on myocardium may differ. We compared the effect of hANP and sodium nitroprusside (SNP) on left ventricular (LV) mechano-energetics in heart failure (HF). Methods Ten patients with HF due to previous myocardial infarction (LV ejection fraction: 45 ± 3%) were instrumented with conductance and coronary sinus thermodilution catheters. LV contractility ( E es : slope of end-systolic pressure–volume relation) and the ratio of LV stroke work (SW) to myocardial oxygen consumption (SW/MVO 2 = mechanical efficiency) were measured in response to intravenous infusion of ANP (0.05 μg/kg/min) or SNP (0.3 μg/kg/min) to lower blood pressure by at least 10 mmHg, and changes in plasma cGMP. Results SNP had no effect on E es , SW, or MVO 2 , thus SW/MVO 2 remained unchanged (40.54 ± 5.84% to 36.59 ± 5.72%, p = 0.25). ANP increased E es , and decreased MVO 2 with preserved SW, resulting in improved SW/MVO 2 (40.49 ± 6.35% to 50.30 ± 7.96%, p = 0.0073). Infusion of ANP (10.42–34.95 pmol/ml, p = 0.0003) increased cGMP levels, whereas infusion of SNP had no effect (10.42–12.23 pmol/ml, p = 0.75). Conclusions Compared to SNP, the ANP-dependent increase in cGMP may ameliorate myocardial inotropy and energetics in HF.

The objective of this study was to investigate the impact of sodium glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV) diastolic function of type 2 diabetes mellitus (T2DM) patients with heart failure (HF). This trial was a prospective multicenter study of 58 T2DM patients

Purpose: Tissue autofluorescence study is a promising means of endoscopic detection of colonic neoplasia, but the mechanism of autofluorescence eruption has still not been verified. The purpose of this study was to precisely analyze the autofluorescence characteristics of freshly prepared normal rat colon under UVA and violet light excitation. Methods: Excised rat colons were studied by using multichannel spectrophotometry, spectroscopic imaging, confocal microscopy, combined two-photon excited fluorescence and second-harmonic generation (SHG) microscopy, and fluorescence lifetime imaging microscopy. Results: Spectroscopic analysis of freshly prepared colon sections revealed that the mucosa and the submucosa showed strong autofluorescence under UVA and violet light excitation. The combined images of two-photon and SHG microscopy revealed that the mucosal epithelia are the important source of autofluorescence. Nicotinamide adenine dinucleotide seems to be one of the major substances involved in the autofluorescence of the mucosal layer on 365- nm light excitation. The autofluorescence spectra of the luminal surfaces were identical to those of the mucosa on crosssectional examinations with 365-nm excitation. The main origin of autofluorescence of the luminal surface with 365-nm excitation is the epithelial cells in the mucosa without overlay of submucosal fluorescence. Conclusions: The mucosal layer is the important source of the autofluorescence observed under excitation with UVA/violet light in multilayered colonic structures. Illumination of 365-nm wavelength light is a suitable means of analyzing the autofluorescence of mucosal epithelia.

Summary Objectives This study was designed to determine the prognostic importance of left ventricular (LV) myocardial stiffness, a hemodynamic index which is closely related to B-type natriuretic peptide (BNP) concentration in patients with congestive heart failure (CHF). Background While elevated BNP, an abnormality of cardiac neurohormones, is known to be an independent marker of death or re-admission, it remains to be clarified whether there is also a strong predictor directly related to cardiac dysfunction. Methods LV performance variables and stress–strain analyses including diastolic myocardial stiffness constant (Km) were obtained from 37 patients with initial CHF by the combined simultaneous measurement of echocardiographic and hemodynamic data. Survivors were monitored for a mean of 23 months, with the main endpoint being combined death or first re-admission for CHF. Results Ten patients (27%) were primary endpoint cases. Both Km and plasma BNP levels were higher in the event than in the event-free group. By Cox proportional hazards analysis, Km ≥ 4.0 was identified as the only variable with significant and independently incremental predictive power to affect the primary endpoint (adjusted hazard ratio = 7.354, 95% confidence interval 1.379–39.232, p = 0.02). Conclusions In patients with CHF, increased myocardial stiffness may have greater prognostic significance compared to other conventional predictors. Increased myocardial stiffness may be considered to be an important prognostic factor independent of the loading conditions.

Background Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to β-adrenergic receptor stimulation. However, the physiological effects of NO on the β-adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure. Methods and Results The study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV external work (EW), pressure - volume area (PVA), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during colforsin daropate infusion, and during concurrent infusion of colforsin daropate with the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA; 200 μmol). Colforsin daropate increased Emax by 53% and EW by 18%, and reduced PVA by 14%, without altering MVO2 or mechanical efficiency. The combination of colforsin daropate with L-NMMA further increased Emax by 26% and reduced PVA by 9%, without altering MVO2 or mechanical efficiency. Conclusions These findings suggest endogenous NO may modulate β-adrenergic post-receptor pathways and preserve myocardial efficiency in patients with IDC. (Circ J 2007; 71: 1268 - 1273)

Serotonin (5HT) can induce coronary artery spasm (CAS) in patients with variant angina (VA). We have previously reported that 5HT(1B) and 5HT(2A) receptors gene were expressed in human coronary arterial smooth muscle cells and that isolated coronary artery from a patient with VA showed the supersensitivity to sumatriptan (SMT), a 5HT(1B/1D) receptor agonist. The aim of the present study was to determine whether SMT can provoke CAS directly or indirectly through platelet aggregation in patients with VA.We evaluated the effects of intracoronary infusion of graded concentrations of SMT on coronary arteries in 9 patients, including 5 documented VA and 4 participants with atypical chest pain as control.SMT provoked CAS in all patients with VA. SMT could not induce CAS in control. SMT (10(-4) M) caused significant contractions (%diameter of baseline; median [interquartile range], 0 [0-18.4]% in VA, as compared with control (proximal segments; 92.6 [77.9-118.9]%, p0.05 vs. VA, distal segments; 92.9 [65.3-158.5]%, p0.01 vs. VA). In control, minor dilation occurred at SMT concentration up to 10(-5) M. SMT could induce in vitro platelet aggregation neither in healthy subjects nor in patients with VA.These findings suggest that activation of 5HT(1B) receptor by SMT can induce CAS directly in patients with VA without platelet activation. This is the first report directly demonstrating the effect of 5HT(1B) receptor activation on human coronary arteries in vivo.

Aims Plasma brain natriuretic peptide (BNP) concentration increases in proportion to heart failure (HF) severity. Although plasma BNP decreases to a certain level by optimal treatment, there is significant heterogeneity in the baseline value among individuals. The underlying mechanism of the steady-state plasma BNP levels remains still controversial. We investigated the hypothesis that myocardial stiffness ( K m) is a major determinant of the plasma BNP level. Methods and results In 19 patients with diastolic HF [DHF; left ventricular ejection fraction (LVEF)≥45%], 18 with systolic HF (SHF; LVEF

A high prevalence of hepatitis C virus (HCV) infection has been reported among idiopathic dilated cardiomyopathy (DCM) patients. We examined the prevalence of DCM patients with HCV antibody, and the pathophysiological characteristics and responsiveness to neurohormonal antagonism in DCM with HCV. HCV antibodies were determined in 540 patients with cardiac diseases. In 117 DCM patients, clinicopathologic data were evaluated before and 1 year after angiotensin converting enzyme inhibitor and/or beta-blocker (ACE-inhibitor/BB) administration and their prognosis was followed-up for a mean of 72 +/- 41 months. HCV antibodies were found in 12 of 135 DCM patients (8.9%) and in 37 of 405 patients without DCM (9.1%) (P = NS). At baseline, contrary to DCM without HCV, DCM with HCV was associated (P < 0.05) with greater left ventricular (LV) end-diastolic and end-systolic dimension, LV mass, and myocardial diameter in endomyocardial biopsy, and lower % fractional shortening. By multivariate analysis, HCV infection was independently associated with larger LV end-systolic dimension among DCM patients (P = 0.005). The advanced LV dilatation and hypertrophy in DCM with HCV decreased more in response to the ACE-inhibitor/BB therapy compared to DCM without HCV. There were no differences between DCM patients with and without HCV in survival and cardiac event-free rates. In summary, although HCV infection appears not to be the specific cause of DCM, HCV may enhance ventricular remodeling leading to heart failure among DCM patients. Nevertheless, the advanced ventricular remodeling with HCV was adequately reversed by neurohormonal antagonism, and did not lead to an unfavorable outcome.

We present a case of cardiac tamponade that occurred during the course of treatment for severe pre-eclampsia. A 37-year-old woman who underwent cesarean section for severe pre-eclampsia developed cardiac tamponade after delivery. While percutaneous pericardiocentesis temporarily improved her condition, pericardial effusion, dyspnea and tachycardia reappeared 5 days after delivery. A continuous drainage tube placed in the pericardial cavity for 5 days was required to maintain maternal cardiac function. Her clinical course was uneventful after continuous drainage and she was discharged 20 days after delivery. No such causes of symptomatic pericardial effusion were detected in the present case. Physicians should be aware of this complication when dyspnea is accompanied by tachycardia and enlargement of the cardiac silhouette with hypolucent lungs on chest X-ray. Immediate pericardiocentesis is also required to prevent life-threatening cardiac tamponade in such cases.

Background: No-reflow phenomenon is observed in approximately one-third of patients after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and is associated with poor functional and clinical outcomes. On the other hand, the formation of free radicals in vasculature exerts deleterious effects on coronary microcirculation. Hypothesis: We hypothesized that redox state in coronary circulation may play a crucial role in no-reflow phenomenon in AMI. Methods: Consecutive 26 patients with first AMI who underwent primary PCI

We present a case of cardiac tamponade that occurred during the course of treatment for severe pre-eclampsia. A 37-year-old woman who underwent cesarean section for severe pre-eclampsia developed cardiac tamponade after delivery. While percutaneous pericardiocentesis temporarily improved her condition, pericardial effusion, dyspnea and tachycardia reappeared 5 days after delivery. A continuous drainage tube placed in the pericardial cavity for 5 days was required to maintain maternal cardiac function. Her clinical course was uneventful after continuous drainage and she was discharged 20 days after delivery. No such causes of symptomatic pericardial effusion were detected in the present case. Physicians should be aware of this complication when dyspnea is accompanied by tachycardia and enlargement of the cardiac silhouette with hypolucent lungs on chest X-ray. Immediate pericardiocentesis is also required to prevent life-threatening cardiac tamponade in such cases.

Background Plasma brain natriuretic peptide (BNP) is a sensitive and specific marker of left ventricular (LV) function. In the treatment of heart failure, especially in idiopathic dilated cardiomyopathy (IDC), β-blocker (BB) therapy has been established as a powerful strategy. The purpose of this study was to analyze relationships between changes in BNP level and LV function during BB therapy in patients with IDC. Methods In 30 patients with IDC who had already received conventional therapy, measurement for plasma BNP and norepinephrine levels and echocardiographic indices were evaluated before and 2 and 6 months after carvedilol in 21 patients and at baseline and after 6 months in 9 patients who did not receive carvedilol. Results After 6 months carvedilol treatment significantly improved LV end-diastolic dimension (LVEDD) (65 ± 8 to 61 ± 8 mm) and LV ejection fraction (LVEF) (34% ± 13% to 43% ± 12%) with intergroup differences; it significantly decreased BNP (127 ± 113 to 69 ± 92 pg/mL) with no intergroup difference; however, it did not decrease norepinephrine. BNP correlated strongly with LVEDD, LVEF, and LV mass index in carvedilol-treated patients. The degree of change in BNP correlated with that in LVEDD or LVEF 6 months after carvedilol. All 14 patients with decreased or unchanged BNP levels showed an increase in LVEF, and 4 of 7 with a rise in BNP had decreased or unchanged LVEF. According to receiver operating characteristic analysis, the optimal BNP levels for detecting LVEF Conclusion: Plasma BNP levels may accurately reflect alteration in LV function and structure and can be used as a therapeutic indicator for risk stratification in patients with IDC during BB therapy. (Am Heart J 2001;141:925-32.)

Although conventional inotropic agents such as catecholamines increase myocardial oxygen consumption, a newly developed inotropic agent, a Ca2+ sensitizer, may be able to increase cardiac output with less myocardial oxygen consumption. By using right-side heart catheterization, we assessed the ratio of the increase in myocardial oxygen consumption per unit increase in cardiac output during beta-adrenergic receptor stimulation (dobutamine, n = 15), phosphodiesterase inhibition (E-1020, n = 10), and Ca2+ sensitization (MCI-154, n = 17) in patients with coronary artery disease. Dobutamine increased cardiac output and myocardial oxygen consumption. E-1020 increased cardiac output but did not change myocardial oxygen consumption. MCI-154 increased cardiac output and decreased myocardial oxygen consumption. The oxygen cost of increasing cardiac output with dobutamine and with E-1020 was different from that with dextran infusion (n = 18); in contrast, the oxygen cost with MCI-154 was significantly smaller. Thus a newly developed Ca2+ sensitizer, MCI-154, may be beneficial for the treatment of heart failure.

Introduction The clinical presentation of eosinophilic myocarditis may vary from asymptomatic to the manifestation of severe symptoms, including cardiac tamponade and arrhythmias. In pregnant patients with this condition, drugs must be used cautiously up to approximately the 4th month of pregnancy because drug use should be limited during the period of fetal organogenesis. Case presentation A 30-year-old Asian woman at 14 weeks of pregnancy with progressive malaise was hospitalized. The electrocardiogram revealed ST elevation and low QRS voltage. Echocardiography revealed massive pericardial effusion and myocardial swelling. A laboratory examination revealed an increase in her white blood cell count, with a predominance of neutrophils. Pericardial drainage was performed for relief of the cardiac tamponade. The pericardial effusion revealed an abundance of eosinophils. Subsequently, the peripheral blood eosinophil count began to rise, and the patient was clinically diagnosed with eosinophilic myopericarditis. The patient’s condition improved rapidly following the initiation of prednisolone treatment, and she finally delivered a full-term normal infant. Conclusions A patient with clinically suspected myopericarditis in the early stage of pregnancy who improved rapidly with pericardial drainage and prednisolone therapy, and successfully delivered a normal full-term infant; the diagnosis was made in the early stage of the disease, based on the detection of an abundance of eosinophils in the pericardial effusion preceding the subsequent development of peripheral blood eosinophilia.

The single-field conductance (SF) method for continuous measurement of left ventricular (LV) volume has achieved widespread use. However, it has been shown theoretically that the ratio between the measured conductance and the actual volume varies between the different interelectrode segments of the catheter due to the convex shape of the equipotential planes at the apex and base. The dual-field conductance (DF) method has recently been introduced and reportedly provides a flatter equipotential plane within the LV. In 11 patients, we compared LV volume measured by biplane cineangiography with conductance volume by the SF and DF methods. Strong correlations were found for both the SF method (r=0.98) and the DF method (r=0.99). However, in comparison with the SF method, the DF method gave a regression line with a slope factor, α, that was closer to unity, and the intercept of the regression line was small (p

Objectives: Recognition of the problems of conventional cardiotonic agents has led to an interest in drugs that produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ (i.e., Ca2+ sensitizing agents). The importance of the effects of these compounds on left ventricular (LV) systolic function has been emphasized, whereas the effect of them on LV diastolic function is still problematic. To investigate the lusitropic action of a novel Ca2+ sensitizing agent, MCI-154, we compared the effects of MCI-154 on LV relaxation and filling dynamics with those of dobutamine in diseased human hearts. Methods: We assessed the slope of the end-systolic pressure-volume relation (Emax), the time constant of LV pressure decay (Tw) and the maximum rate of LV early filling (dV/dtmax) before and after the infusion of dobutamine ( n = 10) or MCI-154 ( n = 9). LV volume and pressure were measured by a conductance catheter and a micro-tip catheter pressure transducer. Results: When both agents increased Emax comparably, dobutamine decreased Tw from 51 to 37 ms and MCI-154 decreased Tw from 54 to 44 ms. The decrease of Tw with MCI-154 was less than that with dobutamine (17 vs. 29%, P < 0.05). At the same time, dobutamine increased dV/dtmax per end-diastolic volume (d V /d t max/ V ) from 2.84 to 3.88 s−1, whereas MCI-154 did not. Conclusions: Diastolic properties were not compromised by MCI-154, though the alteration in them with MCI-154 was less than that with dobutamine when MCI-154 increased LV contractile state to the same extent as dobutamine. The present results suggest that MCI-154 would be an ideal Ca2+ sensitizing agent that enhances force during systole without impairing diastolic function.

To validate the accuracy of human left ventricular (LV) volume measured by the conductance catheter method, conductance volume was compared with LV volume measured by biplane angiography in 19 patients with ischaemic heart disease. Angiographic LV volumes were calculated frame by frame and matched with instantaneous conductance volumes. Calibration was determined by both gain constant, 1/alpha, and parallel conductance, alpha V c. The gain constant, 1/alpha, was the ratio of stroke volume measured by the thermodilution method to that measured by the conductance catheter. The parallel conductance, alpha Vc, was estimated by the saline injection method. There was a good correlation between the corrected conductance volume (Vcc) and the angiographic volume (V angio) such that Vcc = 0.94 V angio + 5.3 ml, r = 0.94, P < 0.001. There were no differences in the correlation coefficients between normal and depressed hearts. Compared with the angiographic data, LV end-diastolic volume, end-systolic volume and ejection fraction were determined accurately by the conductance catheter. We conclude that the conductance catheter method, corrected for gain constant and parallel conductance, can accurately and continuously estimate the LV volume throughout the cardiac cycle in the diseased human heart.

We compared linearity, inotropic sensitivity (using dobutamine) and afterload dependency (using captopril) of contractile indices derived from the end-systolic pressure-volume relationship (ESPVR) and preload recruitable stroke work (PRSW) in man. We investigated 60 patients, 39 with normal (EF > or = 50%, group 1) and 21 with decreased ventricular function (EF < 50%, group 2). Variably loaded P-V loops were constructed by conductance catheters with vena caval occlusions. The slopes of the ESPVR (Emax) and PRSW (Mw) were assessed by linear regression analysis. The correlation coefficients of the ESPVR (r = 0.964) and PRSW (r = 0.976) were both very high, but the Z-value of the ESPVR was lower than for PRSW. During the control period, normalized Emax and Mw were significantly higher in group 1 than group 2 (Emax: 4.6 +/- 2.3 vs 2.8 +/- 0.8 mm Hg ml-1 m-2, Mw: 109 +/- 31 vs 86 +/- 28 10(3) dyn cm-2. After dobutamine, Emax and Mw increased significantly both in group 1 (128% and 124% vs control respectively) and in group 2 (132% and 130% respectively). After captopril, the ESPVR tended to shift to the right with a decrease in afterload; PRSW was unchanged. We conclude that PRSW may be a more linear and reliable index for evaluation of contractility in man.

We compared the oxygen cost of increasing ventricular contractility using Emax (slope of the ventricular end-systolic pressure-volume relation) as the index of ventricular contractility. Contractility was enhanced by calcium and epinephrine in paired experiments on dog left ventricles. Firstly, we obtained left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) of contractions at different volumes in the control contractile state to determine a reference VO2-PVA relation. PVA was obtained as the area in the pressure-volume (P-V) diagram which was bounded by the end-systolic P-V line, end-diastolic P-V curve and systolic P-V trajectory of individual contractions. Secondly, we gradually enhanced Emax with calcium and epinephrine in two consecutive runs at a fixed ventricular volume. Both VO2 and PVA increased with enhanced Emax. From these VO2-PVA data, we calculated the PVA-independent VO2 values at the respective enhanced Emax levels and determined the oxygen cost of Emax as the slope of the relation between the PVA-independent VO2 and Emax. The cost per beat and per 100 g was 0.00158 ml O2/(mmHg/ml) for calcium and 0.00166 ml O2/(mmHg/ml) for epinephrine on average, values not significantly different from each other (P less than 0.05). We conclude that epinephrine and calcium have similar oxygen costs of contractility over a wide range of Emax despite their different pharmacological mechanisms of positive inotropism.

Autofluorescence endoscopy for detection of colonic neoplasia has recently received attention in the field of clinical gastroenterology. Here, we analyzed the characteristics of autofluorescence of the excised normal rat colonic mucosa under UV/violet-light excitation. The results of microscopic measurement showed that the mucosal epithelia were the important source of autofluorescence in the mucosa under UV/violet-light excitation. The fluorescence spectral study revealed that nicotinamide adenine dinucleotide (NADH) seemed to be one of the major substances involved in the autofluorescence of mucosa under UVA light excitation. Our results suggest that the autofluorescence of mucosal epithelia generated by NADH is a major source of the autofluorescence in the mucosal layer under excitation by UVA light.

Autofluorescence endoscopy is a promising modality for diagnosis of colonic tumors. This article discusses the origin of autofluorescence of the normal colon. Excised normal colons were analyzed by using fluorescence stereomicroscopy and a fluorescence-lifetime microscopy system. Fluorescence images showed that the mucosa had stronger autofluorescence than the submucosa. The results of fluorescence-lifetime measurement showed that nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) might be responsible for the autofluorescence of the colonic epithelia. Our results suggest that the mucosal autofluorescence generates by NADH and FAD was an important source of the green autofluorescence.

OBJECTIVE: ss-adrenergic receptors (ssARs) are powerful regulators of cardiac function in vivo, activating heterotrimeric G proteins and the effector molecule adenylyl cyclase (AC). Interestingly, cardiac-specific overexpression of different AC isoforms leads to variable changes in cardiac function. Whether AC overexpression affects intrinsic cardiac contractility in an isoform-specific fashion determining a change in exercise capacity is currently unknown. METHODS: To address this issue, we performed load-independent measurements of cardiac systolic and diastolic function by pressure-volume (PV) loop analysis in intact wild-type mice (WT) and transgenic mice overexpressing the AC isoforms 5 or 8. RESULTS: Here we show that cardiac overexpression of either AC5 or AC8 transgenic mice determined an increase in intrinsic cardiac contractility. Interestingly, AC8 transgenic mice displayed a significantly greater increase in cardiac contractility and improved active phase of relaxation. Despite these differences detected by PV loop analysis, both AC5 and AC8 mice showed a marked increase in exercise capacity on treadmill testing. CONCLUSIONS: Our results demonstrate that load-independent measurements of cardiac function are needed to compare different groups of genetically-modified mouse models and to detect subtle AC isoform-specific changes in cardiac performance.

Cardiac stress consistently activates c-Jun NH(2)-terminal kinase (JNK) pathways, however the role of different members of the JNK family is unclear. In this study, we applied pressure overload (TAC) in mice with selective deletion of the three JNK genes (Jnk1(-/-), Jnk2(-/-), and Jnk3(-/-)). Following TAC, all three JNK knockout mouse lines developed cardiac hypertrophy similar to wild-type mice (WT), but only JNK1(-/-) mice displayed a significant reduction in fractional shortening after 3 and 7 days of pressure overload, associated with a significant increase in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining and marked inflammatory infiltrate. After the acute deterioration stage, JNK1(-/-) mice underwent a slow recovery followed by a steady progression of cardiac dysfunction, becoming indistinguishable from WT after 12 weeks of TAC. These data suggest that JNK1 plays a protective role in response to pressure overload, preventing the early deterioration in cardiac function following an acute increase in afterload.

Background The present multicenter study investigated whether the combination of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) is more beneficial for preventing left ventricular remodeling and suppressing neurohumoral factors than either ACEI or ARB alone. Methods and Results One hundred and six patients with mild-to-moderate congestive heart failure treated in 26 Japanese institutes were randomly assigned to the combination therapy or monotherapy. Changes in physical activity (New York Heart Association functional classes, Specific Activity Scale (SAS)), concentrations of neurohumoral factors (plasma renin activity, angiotensin II, aldosterone, and brain natriuretic peptide (BNP)), and cardiac function for 6 months were compared between the 2 groups. It was found that the combination therapy, which was administered at doses standard in Japan, increased the SAS score (4.5±1.5 to 4.9±1.5, p

Pressure overload cardiac hypertrophy may be a compensatory mechanism to normalize systolic wall stress and preserve left ventricular (LV) function. To test this concept, we developed a novel in vivo method to measure myocardial stress (ς)-strain (ɛ) relations in normal and hypertrophied mice. LV volume was measured using two pairs of miniature omnidirectional piezoelectric crystals implanted orthogonally in the endocardium and one crystal placed on the anterior free wall to measure instantaneous wall thickness. Highly linear ς-ε relations were obtained in control ( n = 7) and hypertrophied mice produced by 7 days of transverse aortic constriction (TAC; n = 13). Administration of dobutamine in control mice significantly increased the load-independent measure of LV contractility, systolic myocardial stiffness. In TAC mice, systolic myocardial stiffness was significantly greater than in control mice (3,156 ± 1,433 vs. 1,435 ± 467 g/cm2, P < 0.01), indicating enhanced myocardial contractility with pressure overload. However, despite the increased systolic performance, both active (time constant of LV pressure decay) and passive (diastolic myocardial stiffness constant) diastolic properties were markedly abnormal in TAC mice compared with control mice. These data suggest that the development of cardiac hypertrophy is associated with a heightened contractile state, perhaps as an early compensatory response to pressure overload.

Background — A long-standing hypothesis has been that hypertrophy is compensatory and by normalizing wall stress acts to maintain normal cardiac function. Epidemiological data, however, have shown that cardiac hypertrophy is associated with increased mortality, thus casting doubt on the validity of this hypothesis. Methods and Results — To determine whether cardiac hypertrophy is necessary to preserve cardiac function, we used 2 genetically altered mouse models that have an attenuated hypertrophic response to 8 weeks of pressure overload. End-systolic wall stress (ς es ) obtained by sonomicrometry after 1 week of pressure overload showed complete normalization of ς es in pressure-overloaded wild-type mice (287±39 versus sham, 254±34 g/cm 2 ), whereas the blunted hypertrophic response in the transgenic mice was inadequate to normalize ς es (415±81 g/cm 2 , P es , cardiac function as measured by serial echocardiography showed little deterioration in either of the pressure-overloaded genetic models with blunted hypertrophy. In contrast, wild-type mice with similar pressure overload showed a significant increase in chamber dimensions and progressive deterioration in cardiac function. Analysis of downstream signaling pathways in the late stages of pressure overload suggests that phosphoinositide 3-kinase may play a pivotal role in the transition from hypertrophy to heart failure. Conclusions — These data suggest that under conditions of pressure overload, the development of cardiac hypertrophy and normalization of wall stress may not be necessary to preserve cardiac function, as previously hypothesized.

Background Stimulation of β 1 - and β 2 -adrenergic receptors (ARs) in the heart results in positive inotropy. In contrast, it has been reported that the β 3 AR is also expressed in the human heart and that its stimulation leads to negative inotropic effects. Methods and Results To better understand the role of β 3 ARs in cardiac function, we generated transgenic mice with cardiac-specific overexpression of 330 fmol/mg protein of the human β 3 AR (TGβ 3 mice). Hemodynamic characterization was performed by cardiac catheterization in closed-chest anesthetized mice, by pressure-volume-loop analysis, and by echocardiography in conscious mice. After propranolol blockade of endogenous β 1 - and β 2 ARs, isoproterenol resulted in an increase in contractility in the TGβ 3 mice (30%), with no effect in wild-type mice. Similarly, stimulation with the selective human β 3 AR agonist L-755,507 significantly increased contractility in the TGβ 3 mice (160%), with no effect in wild-type mice, as determined by hemodynamic measurements and by end-systolic pressure-volume relations. The underlying mechanism of the positive inotropy incurred with L-755,507 in the TGβ 3 mice was investigated in terms of β 3 AR–G-protein coupling and adenylyl cyclase activation. Stimulation of cardiac membranes from TGβ 3 mice with L-755,507 resulted in a pertussis toxin–insensitive 1.33-fold increase in [ 35 S]GTPγS loading and a 1.6-fold increase in adenylyl cyclase activity. Conclusions Cardiac overexpression of human β 3 ARs results in positive inotropy only on stimulation with a β 3 AR agonist. Overexpressed β 3 ARs couple to G s and activate adenylyl cyclase on agonist stimulation.

Background —The results of recent studies suggest that NO synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to β-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular (LV) contractile response to β-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. Methods and Results —We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined LV contractility (E max , the slope of end-systolic pressure-volume relation), LV external work (EW), myocardial oxygen consumption (MV̇ o 2 ), and mechanical efficiency (measured as EW/MV̇ o 2 ) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4.8±0.3 μg · kg −1 · min −1 IV). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor N G -monomethyl- l -arginine (L-NMMA; 200 μmol). DOB increased E max , EW, and MV̇ o 2 (by 77±17%, 39±5%, and 21±5%, respectively), leading to an increase in mechanical efficiency (25.4±3.1% to 29.6±4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased E max , EW, and MV̇ o 2 (by 140±21%, 64±9%, and 35±5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3±3.3% to 29.5±4.5%) because EW and MV̇ o 2 increased in parallel. Conclusions —These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MV̇ o 2 through attenuation of LV contractile response to β-adrenergic stimulation while maintaining LV energy-converting efficiency.

Beta-blocker therapy has been shown to improve cardiac function and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). However, whether beta-blockers reduce severe ventricular arrhythmias and sudden cardiac death has not been clarified. The present study was designed to investigate the effects of beta-blockers on non-sustained ventricular tachycardia (VT) and sudden cardiac death in patients with DCM. Sixty-five patients with DCM treated with diuretics, digitalis and angiotensin-converting enzyme inhibitors were assigned to receive beta-blockers (n = 33) or not (n = 32). Mean follow-up was 53+/-30 months. The echocardiographic indices of cardiac function, the incidence of non-sustained VT on Holter monitoring electrocardiograms, and sudden cardiac death rate were compared between the 2 groups. Comparable improvement in cardiac function on echocardiograms was found in the 2 treatment groups. The patient group treated with beta-blockers showed a significant reduction in the prevalence of VT (from 43 to 15%, p

To test the hypothesis that coronary spasm could be a coronary manifestation of systemic endothelial dysfunction and that the activity of coronary spasm could influence systemic endothelial function, we examined brachial flow-mediated, endothelium-dependent vasodilation and nitroglycerin-induced endothelium-independent vasodilation with high-resolution ultrasound in 11 men with variant angina pectoris (6 active and 5 inactive) without established coronary atherosclerosis. Endothelium-dependent vasodilation in peripheral circulation was preserved in men with active and inactive variant angina pectoris, suggesting that systemic endothelial dysfunction is not involved in either the pathogenesis or the activity of coronary spasm.

It has been shown recently that the force-frequency relationship is blunted in experimental heart failure models. Furthermore, tachycardia is thought to have adverse effects on the diseased heart for several reasons, one of which is an increase in myocardial oxygen consumption. Inversely, the oxygen-saving effects of bradycardia may be beneficial for the treatment of heart failure. The aim of this study was to elucidate how heart rate (HR) modulates cardiac mechanics and energetics in patients with left ventricular (LV) dysfunction. LV pressure-volume data and myocardial oxygen consumption (MVO2) was assessed using conductance and coronary sinus thermodilution catheters in 14 patients with moderate LV dysfunction (mean ejection fraction 34%) under 3 conditions: (a) basal, (b) HR increased by 20% using atrial pacing, and (c) HR decreased by 16% using a specific bradycardic agent, zatebradine (7.5 mg po). Atrial pacing decreased external work (EW) (from 0.39 to 0.31 J beat-1 m-2, p

Some recent trials have shown that angiotensin-converting enzyme (ACE) inhibitors and/or beta blockers can improve left ventricular (LV) function and decrease LV mass in patients with idiopathic dilated cardiomyopathy (IDC). We assessed the prevalence and predictors of patients with IDC that showed marked reverse remodeling (a decrease in LV end-diastolic dimensionor = 5 mm to a final LV end-diastolic dimensionor = 55 mm and an increase in percent LV fractional shorteningor = 5% to a final percent fractional shortening ofor = 25% and a decrease in LV massor = 10%) after 2 years of intensive therapy with ACE inhibitors and/or beta blockers. In 78 patients with IDC (mean age 51 +/- 14 years), the clinical, echocardiographic, hemodynamic, laboratory, and endomyocardial biopsy data were evaluated at diagnosis and serial echocardiography was performed for 2 years. After 2 years of therapy, 20 of 78 patients (26%) showed marked reverse remodeling. Multivariate analysis revealed that higher systolic blood pressure (135 +/- 17 vs 120 +/- 16 mm Hg, p0.001) and lower pulmonary arterial wedge pressure (7 +/- 3 vs 12 +/- 8 mm Hg, p0.01) at diagnosis were independent predictors of reverse remodeling. Then, we further analyzed the prognosis of these patients for a mean of 50 +/- 32 months; 5-year survival (p0.02) and event-free rates (p = 0.001) were better in patients with reverse remodeling than in patients without reverse remodeling.

Objectives. The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Background. Unlike conventional cardiotonic agents, a Ca2+sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. Methods. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2were assessed before and after infusion of MCI-154 or dobutamine. The PVA-independent Vo2(Vo2mainly for excitation-contraction coupling) was assessed as the Vo2at zero PVA. Results. Both agents increased Emax comparably (dobutamine: from 3.55 ± 1.10 [mean ± SD] to 5.04 ± 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 ± 1.26 to 5.37 ± 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2(from 0.22 ± 0.08 to 0.27 ± 0.09 ml O2, p < 0.05) and PVA-independent Vo2(from 0.019 ± 0.019 to 0.091 ± 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (ΔPVA-independent Vo2/ΔEmax) was less with MCI-154 than with dobutamine (0.14 ± 0.18 vs. 1.10 ± 0.80 J/mm Hg per ml per m2, p < 0.05). Conclusions. These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents. (J Am Coll Cardiol 1997;29:613–22)

Background The negative chronotropic effect of β-blocking agents is likely to provide hemodynamic and energetic advantages. However, the negative chronotropic effect on cardiac energetics observed on the initiation of β-blockade therapy has not been fully elucidated. Methods and Results In 18 patients with heart failure, left ventricular pressure and volume, external work (EW), myocardial oxygen consumption per beat (total V̇ o 2 ), mechanical efficiency (EW/total V̇ o 2 ), and V̇ o 2 for nonmechanical work (total V̇ o 2 −2·EW) were measured with the use of conductance catheter and Webster catheter at the following three states: under control conditions and after β-blockade (0.15±0.07 mg/kg propranolol IV) with and without atrial pacing to keep the heart rate at control levels. Heart rate decreased after atrial pacing was stopped. EW decreased during β-blockade with pacing and returned to the control level after pacing was stopped. Total V̇ o 2 did not change during β-blockade with or without pacing, whereas V̇ o 2 for nonmechanical work increased with pacing and returned to the control level after pacing was stopped. As a result, mechanical efficiency decreased during β-blockade with pacing and returned to the control level after pacing was stopped. Conclusions The negative chronotropic effect of a β-blocking agent may offset the mechanoenergetical deterioration resulting from its negative inotropic effect through a reduction in oxygen expenditure for nonmechanical work. These findings suggest that the negative chronotropic effect is an important aspect of β-blockade therapy.

For the treatment of heart failure, inotropic agents yield short-term hemodynamic improvement. However, inotropic therapy is still an unfilled promise for the treatment of chronic heart failure (1). This may partly result from the fact that inotropic interventions increase myocardial oxygen consumption (VO2). Therefore, the investigation of myocardial energetics in relation to inotropic agents in patients with heart disease has clinical and therapeutic relevance. Recently, the concept of left ventricular (LV) elastance (Emax) and systolic pressure-volume area (PVA) has been proposed by Suga and his colleagues (2,3,4,5). Experimental studies have shown that the relation between VO2 and PVA is linear under a variety of loading conditions. This linear relation has been used to partition VO2 into non-mechanical and mechanical portions. Experimental studies have shown that positive inotropic interventions, which enhance Emax, shift the VO2-PVA relation line upward in a parallel manner. The resultant increase in VO2 intercept of the relation has been considered to be VO2 for non-mechanical work. The relation between Emax and PVA-independent VO2 has been reported to be linear; the slope represents “oxygen cost of contractility” under various inotropic interventions. The aim of this study was to examine the effects of various inotropic agents on human cardiac mechanoenergetics by utilizing the concept of Emax and the VO2-PVA relation. To this end, we compared the effects of the newly developed phosphodiesterase inhibitor E-1020 and a novel Ca++ sensitizing agent, MCI-154, with dobutamine in patients with heart disease.

Studies reported in the literature show that the stroke work (SW) versus end-diastolic volume (Ved) relationship, namely, the preload recruitable stroke work relation (PRSW), is experimentally linear in closed-chest dog hearts and its slope reflects left ventricular contractility. We considered the theoretical cardiodynamic conditions necessary for the linearity of the SW-Ved relation by utilizing ventricular end-systolic elastance, Emax (ventricular contractility), and effective arterial elastance, Ea (arterial afterload). We simulated the SW-Ved relation, using four theoretical models of the left ventricle, as follows: Ea is constant and the end-systolic pressure-volume relation (ESPVR) is linear (model 1), or nonlinear (model 2), and Ea is variable and ESPVR is linear (model 3), or nonlinear (model 4). The results show that the SW-Ved relation can be linear in both linear and nonlinear ESPVR models (models 3 and 4) only when Ea is variable. In these models, end-systolic pressure (Pes) and Ea should gradually fall, maintaining the stroke volume (SV) relatively constant with decreases in Ved until the low end of the physiological Ved range. Then, Ea should rise sharply so that Pes does not fall below the critical level. These results suggest that the autoregulation mechanisms of an intact animal operate to adapt the arterial afterload against acute changes in LV preload, maintaining cardiac output and coronary artery pressure. Such mechanisms may thus produce a linear SW-Ved relation over a wide range of conditions.

We examined the effects of a novel water-soluble forskolin derivative, NKH477 (0.5 microgram/kg/min), on arterial-ventricular (A-V) coupling and mechanical energy transduction from heart to circulatory bed in comparison with those of dobutamine (3 micrograms/kg/min) in 8 patients with left ventricular (LV) systolic dysfunction using a conductance catheter method. A-V coupling was assessed as the ratio of the effective arterial elastance (E(a)) to the slope of the end-systolic pressure-volume relation (ESPVR) (E(max), left ventricular contractility index), and the ratio of mechanical energy transduction was obtained as the fraction of PV area (PVA) comprised of stroke work (SW). E(max) (2.59 mm Hg/ml/m2), E(a)/E(max) (1.62), and SW/PVA (0.58) were impaired in control contractile state. NKH477 increased Emax to the same extent as dobutamine. E(a) decreased with NKH477 but not with dobutamine. As a consequence, the decrease in E(a)/E(max) with NKH477 was greater than that with dobutamine (52 vs. 47%, p0.05); the increase in SW/PVA with NKH477 was also greater than that with dobutamine (28 vs. 21%, p0.05). These findings suggest that NKH477 may be a superior alternative to dobutamine in A-V coupling and mechanical energy transduction in patients with LV systolic dysfunction.

Objective: The aim was to characterise the impaired myocardial mechanoenergetics in patients with heart failure due to old myocardial infarction by using the oxygen consumption versus left ventricular pressure – volume area (PVA) relationship. Methods: The ![Graphic][1] o2-PVA relationship was assessed in 15 patients: group N consisted of seven patients with vasospastic angina pectoris whose left ventricular ejection fractions were normal [72(SD 8)%], and group F consisted of eight patients with old myocardial infarction whose left ventricular ejection fractions were reduced [45(11)%]. Left ventricular volume and pressure were measured by the conductance catheter method. ![Graphic][2] o2was measured by thermodilution. Results: Linear ![Graphic][3] o2-PVA relationships with dextran infusions were obtained in both groups (median r = 0.92 v 0.90). There was no difference in the slope between the two groups. There was a positive correlation between Emax and Vo2 at median PVA (Vo2.PVAO.8) in group N. Emax an index of left ventricular contractility, was significantly smaller in group F than in group N, at 5.1(2.1) v 3.2(1.1) mm Hg·ml−1·m2 p

To validate the usefulness of the conductance catheter in the clinical setting, we first studied the accuracy of human left ventricular (LV) volume measured by conductance catheter in comparison with LV volume measured by biplane angiography in 19 patients with heart disease. Secondly, we made a comparison of end-systolic pressure volume relation (ESPVR) and preload recruitable stroke work (PRSW) relation in 60 patients with heart disease. Thirdly, we studied the myocardial oxygen consumption (VO2)-pressure volume area (PVA) relation to assess contractile efficiency in 22 patients with heart disease. There was a good correlation between the corrected conductance volume (Vcc) and the angiographic volume (V angio) (Vcc = 0.94 Vangio + 5.4, r = 0.94, P less than 0.001). Two relations, ESPVR and PRSW, were well described by straight lines with high correlation coefficients. However, PRSW was a more linear contractile index than ESPVR. The reciprocal of the slope of the VO2-PVA relation was approximately 40% in the control contractile state. We conclude that the conductance catheter accurately measures LV volumes and facilitates the assessment of ESPVR, PRSW and contractile efficiency in human LV.