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Left ventricular assist device (LVAD) has been saving many lives in patients with severe left ventricular (LV) failure. Recently, a minimally invasive transvascular LVAD such as Impella enables us to support unstable hemodynamics in severely ill patients. Although LVAD support increases total LV cardiac output (COTLV) at the expense of decreases in the native LV cardiac output (CONLV), the underlying mechanism determining COTLV remains unestablished. This study aims to clarify the mechanism and develop a framework to predict COTLV under known LVAD flow (COLVAD). We previously developed a generalized framework of circulatory equilibrium that consists of the integrated CO curve and the VR surface as common functions of right atrial pressure (PRA) and left atrial pressure (PLA). The intersection between the integrated CO curve and the VR surface defines circulatory equilibrium. Incorporating LVAD into this framework indicated that LVAD increases afterload, which in turn decreases CONLV. The total LV cardiac output (COTLV) under LVAD support becomes COTLV = CONLV+EFe · COLVAD, where EFe is effective ejection fraction, i.e., Ees/(Ees+Ea). Ees and Ea represent LV end-systolic elastance (Ees) and effective arterial elastance (Ea), respectively. In other words, LVAD shifts the total LV cardiac output curve upward by EFe · COLVAD. In contrast, LVAD does not change the VR surface or the right ventricular CO curve. In six anesthetized dogs, we created LV failure by the coronary ligation of the left anterior descending artery and inserted LVAD by withdrawing blood from LV and pumping out to the femoral artery. We determined the parameters of the CO curve with a volume-change technique. We then changed the COLVAD stepwise from 0 to 70–100 ml/kg/min and predicted hemodynamics by using the proposed circulatory equilibrium. Predicted COTLV, PRA, and PLA for each step correlated well with those measured (SEE; 2.8 ml/kg/min 0.17 mmHg, and 0.65 mmHg, respectively, r2; 0.993, 0.993, and 0.965, respectively). The proposed framework quantitatively predicted the upward-shift of the total CO curve resulting from the synergistic effect of LV systolic function and LVAD support. The proposed framework can contribute to the safe management of patients with LVAD.

Left ventricular assist device (LVAD) saves lives in patients with severe left ventricular (LV) failure. However, predicting how much LVAD boosts total cardiac output (CO) remains difficult. This study aimed to develop a framework to quantitatively predict the impact of LVAD on hemodynamics. We adopted the circulatory equilibrium framework and incorporated LVAD into the integrated CO curve to derive the circulatory equilibrium. In anesthetized dogs, we ligated left coronary arteries to create LV failure and inserted a centrifugal pump as LVAD. Using CO and right (PRA) and left atrial pressure (PLA) measured before LVAD support, we predetermined the stressed volume (V) and logarithmic slope of right heart CO curve (SR). Next, we initiated LVAD at maximum level and then decreased LVAD flow stepwise while monitoring hemodynamic changes. We predicted LVAD-induced CO and PRA for given PLA from the predetermined SR and V and compared with those measured experimentally. The predicted CO [ r2 = 0.907, SE of estimate (SEE) = 5.59 ml·min−1·kg−1, P < 0.001] and PRA ( r2 = 0.967, SEE = 0.307 mmHg, P < 0.001) matched well with measured values indicating the validity of the proposed framework. We further conducted simulation using the validated framework to analyze the impact of LVAD on PRA under various right ventricular (RV) functions. It indicated that PRA is relatively insensitive to changes in RV end-systolic elastance or pulmonary arterial resistance, but sensitive to changes in V. In conclusion, the circulatory equilibrium framework predicts quantitatively the hemodynamic impact of LVAD. This knowledge would contribute to safe management of patients with LV failure undergoing LVAD implantation. NEW & NOTEWORTHY Hemodynamic response to left ventricular assist device (LVAD) has not been quantitatively investigated. This is the first report of quantitative prediction of the hemodynamics on LVAD using circulatory equilibrium framework. The validated framework allows us to simulate the impact of LVAD on right atrial pressure under various right ventricular functions.

Reducing myocardial damage is a prerequisite to prevent chronic heart failure after acute myocardial infarction (AMI). Although vagal nerve stimulation (VNS) has been repeatedly demonstrated to have potent anti-infarct effect, technical difficulties have precluded its clinical application. We developed a novel therapeutic strategy of intravenous VNS (iVNS) and examined whether iVNS administered prior to coronary reperfusion in a canine AMI model reduces infarct size and prevents heart failure.In 35 mongrel dogs, we induced ischemia by ligating the left anterior descending coronary artery and then reperfused 3h later (I/R). We transvenously placed a catheter electrode in the superior vena cava and adjusted the stimulation intensity to a level that induced bradycardia but maintained stable hemodynamics (continuous, 5.1±2.1V, 10Hz). We administered iVNS from onset (iVNS-0, n=7) or 90min after onset (iVNS-90, n=7) of ischemia until one hour after reperfusion. Four weeks after ischemia-reperfusion, iVNS markedly reduced infarct size (iVNS-0: 2.4±2.1%, p0.05 and iVNS-90: 4.5±4.5%, p0.05) compared with I/R control (I/R: 13.3±2.5%), and improved cardiac performance and hemodynamics. Atrial pacing (n=7) to abolish iVNS-induced bradycardia significantly attenuated the beneficial effects of iVNS.Short-term iVNS delivered prior to coronary reperfusion markedly reduced infarct size and preserved cardiac function one month after AMI. The bradycardic effect plays an important role in the beneficial effect of iVNS. How other mechanisms contribute to the reduction of infarct size remains to be studied.

Background Eosinophilic myocarditis is characterized by myocardial eosinophilic infiltration and is largely associated with hypereosinophilia. However, eosinophilic myocarditis with a normal peripheral eosinophilic count has been previously reported. Since the absence of eosinophilia poses a challenge for therapeutic management, we evaluated whether troponin I (TnI) levels can be used in the management of eosinophilic myocarditis where peripheral eosinophilia is absent. Case summary We report the case of a 77-year-old woman who developed cardiogenic shock due to acute necrotizing eosinophilic myocarditis, which required mechanical circulatory support. She did not have hypereosinophilia, but endomyocardial biopsy confirmed massive infiltration of eosinophils into the myocardium. We administered high-dose corticosteroids for 3 days and she dramatically improved. Along with this, the TnI level, which was elevated at the time of patient presentation, also decreased after steroid therapy. Troponin I level did not increase again without taking any oral prednisolone, and the follow-up biopsy after 6 months showed complete recovery of eosinophilic myocarditis. Discussion Troponin I-guided treatment is a useful tool in the management of eosinophilic myocarditis because it helps with therapeutic decisions, especially in the absence of eosinophilia.

Background: Acute myocardial infarction remains a leading cause of chronic heart failure. Excessive myocardial oxygen demand relative to supply is the fundamental mechanism of myocardial infarction. We thus hypothesized that left ventricular (LV) mechanical unloading by the total support of transvascular LV assist device Impella could minimize oxygen demand, thereby reducing infarct size and preventing subsequent heart failure. Methods and Results: In 20 dogs, we ligated the left anterior descending coronary artery for 180 minutes and then reperfused. We introduced Impella from 60 minutes after the onset of ischemia to 60 minutes after reperfusion. In the partial support group, Impella supported 50% of total cardiac output. In the total support group, systemic flow totally depends on Impella flow. Four weeks after ischemia/reperfusion (I/R), we compared LV function and infarct size among 4 groups: sham (no I/R), I/R (no Impella support), partial support, and total support. Compared with I/R, total support lowered LV end-diastolic pressure (15.0±3.5 versus 4.7±1.7 mm Hg; P P P P Conclusions: LV mechanical unloading by the total support of Impella during the acute phase of myocardial infarction reduced infarct size and prevented subsequent heart failure in dogs.

Background: We previously showed that volume loading activates low pressure baroreflex (L-BARO) and causes biphasic change in sympathetic nerve activity (SNA). We examine if chronic heart failure (...

Background: Vagal nerve stimulation (VNS) in AMI is known to have a powerful anti-ischemic effect, but the technical difficulties associated with VNS limit its application under emergency settings....

Baroreflex modulates both the ventricular and vascular properties and stabilizes arterial pressure (AP). However, how changes in those mechanical properties quantitatively impact the dynamic AP regulation remains unknown. We developed a framework of circulatory equilibrium, in which both venous return and cardiac output are expressed as functions of left ventricular (LV) end-systolic elastance (Ees), heart rate (HR), systemic vascular resistance (R), and stressed blood volume (V). We investigated the contribution of each mechanical property using the framework of circulatory equilibrium. In six anesthetized dogs, we vascularly isolated carotid sinuses and randomly changed carotid sinus pressure (CSP), while measuring the LV Ees, aortic flow, right and left atrial pressure, and AP for at least 60 min. We estimated transfer functions from CSP to Ees, HR, R, and V in each dog. We then predicted these parameters in response to changes in CSP from the transfer functions using a data set not used for identifying transfer functions and predicted changes in AP using the equilibrium framework. Predicted APs matched reasonably well with those measured ( r2 = 0.85–0.96, P < 0.001). Sensitivity analyses indicated that Ees and HR (ventricular properties) accounted for 14 ± 4 and 4 ± 2%, respectively, whereas R and V (vascular properties) accounted for 32 ± 4 and 39 ± 4%, respectively, of baroreflex-induced AP regulation. We concluded that baroreflex-induced dynamic AP changes can be accurately predicted by the transfer functions from CSP to mechanical properties using our framework of circulatory equilibrium. Changes in the vascular properties, not the ventricular properties, predominantly determine baroreflex-induced AP regulation.

It has been established that vagal nerve stimulation (VNS) benefits patients and/or animals with heart failure. However, the impact of VNS on sympathetic nerve activity (SNA) remains unknown. In this study, we investigated how vagal afferent stimulation (AVNS) impacts baroreflex control of SNA. In 12 anesthetized Sprague–Dawley rats, we controlled the pressure in isolated bilateral carotid sinuses (CSP), and measured splanchnic SNA and arterial pressure (AP). Under a constant CSP, increasing the voltage of AVNS dose dependently decreased SNA and AP. The averaged maximal inhibition of SNA was ‐28.0 ± 10.3%. To evaluate the dynamic impacts of AVNS on SNA, we performed random AVNS using binary white noise sequences, and identified the transfer function from AVNS to SNA and that from SNA to AP. We also identified transfer functions of the native baroreflex from CSP to SNA (neural arc) and from SNA to AP (peripheral arc). The transfer function from AVNS to SNA strikingly resembled the baroreflex neural arc and the transfer functions of SNA to AP were indistinguishable whether we perturbed ANVS or CSP, indicating that they likely share common central and peripheral neural mechanisms. To examine the impact of AVNS on baroreflex, we changed CSP stepwise and measured SNA and AP responses with or without AVNS. AVNS resets the sigmoidal neural arc downward, but did not affect the linear peripheral arc. In conclusion, AVNS resets the baroreflex neural arc and induces sympathoinhibition in the same manner as the control of SNA and AP by the native baroreflex., Afferent vagal nerve stimulation resets the baroreflex neural arc and inhibits sympathetic nerve activity.

Although venoarterial extracorporeal membrane oxygenation (ECMO) was developed to rescue patients with cardiogenic shock, the impact of ECMO on hemodynamics is often unpredictable and can lead to hemodynamic collapse. In this study, we developed a framework in which we incorporated ECMO into the extended Guyton's model of circulatory equilibrium and predicted hemodynamic changes in response to ECMO. We first determined the cardiac output (CO) curves of left and right heart (to generate the integrated CO curve) without ECMO in eight normal and seven dogs with left ventricular dysfunction. Using the CO curves obtained and standard parameters for the venous return surface, we predicted the circulatory equilibrium under various levels of ECMO support. The predicted total flow (native left heart flow plus ECMO flow), right atrial pressure (PRA), and left atrial pressure (PLA) matched well with those measured [total flow: coefficient of determination ( r2) = 0.99, standard error of estimate (SEE) = 5.8 ml·min−1·kg−1, PRA: r2 = 0.95, SEE = 0.23 mmHg, PLA: r2 = 0.99, SEE = 0.59 mmHg]. Lastly, we estimated the CO curves under ECMO support from minute changes in hemodynamics induced by change in ECMO. From the CO curves estimated, we predicted the circulatory equilibrium. The predicted total flow ( r2 = 0.93, SEE = 0.5 ml·min−1·kg−1), PRA ( r2 = 0.99, SEE = 0.54 mmHg), and PLA ( r2 = 0.95, SEE = 0.89 mmHg) matched reasonably well with those measured. A numerical simulation indicated that ECMO support may cause pulmonary edema, if right ventricular function is compromised. We conclude that the proposed framework may enhance the benefit and reduce the risk of ECMO support in patients with critical hemodynamic conditions.

Background: Although volume loading activates the low pressure baroreflex (LBR), its quantitative impact on sympathetic nerve activity (SNA) and arterial baroreflex (ABR) remains unknown. The aim of this study is to clarify how the LBR affects SNA and ABR. Methods/Results: In 10 anesthetized rats, we isolated carotid sinuses and controlled carotid sinus pressure (CSP). We infused dextran to activate LBR. We measured central venous pressure (CVP) and SNA. We fixed CSP at 90mmHg to abolish ABR. We infused dextran of 5% blood volume stepwise with or without vagotomy. In the low CVP range (2.6±0.8 to 4.5±0.7mmHg), volume loading increased SNA as much as 64.8±19.5% from the baseline, while further volume loading in the high CVP range (4.5±0.7 to 7.0±0.8 mmHg) returned SNA to the baseline level. Bilateral vagotomy totally abolished those changes in SNA. To assess the impact of LBR on the ABR central system, we changed CSP stepwise from 60 to 160 mmHg at the normal volume, mild volume loading and high volume loa...

Background: The hypersensitive peripheral chemoreflex induces sympathoexcitation and vagolysis and is known to associate with the poor prognosis of chronic heart failure (CHF). We hypothesized that denervation of carotid body (CBD) improves CHF and restore the normal autonomic balance in a rat model of myocardial infarction (MI)-induced CHF. Methods: We created MI-induced CHF in rats. Surviving rats at 4 weeks after MI were randomized into CBD (n=10) and sham-operated (Sham; n=10) group. To establish CBD, we removed the tissues around the carotid bifurcation. Two months after CBD, we evaluated physiological and histological findings. Results: CBD significantly reduced biventricular weight (2.9±0.1 vs. 3.3±0.1 g/kg, p

Background: Although VNS is known to have a powerful anti-infarct effect, the technical difficulty associated with VNS precludes its application under emergent settings of AMI. We developed a novel...

Background Because the prevalence of coronary artery calcification is lower among Japanese than among Western individuals, aspects of the Japanese lifestyle might be related to the development of calcification. We aimed to clarify the relationship between coronary artery calcium scores in Japanese patients and various lifestyle factors among the Japanese population. Methods Study subjects were patients aged ≥20 years who underwent multidetector-row computed tomography. A total of 201 patients agreed to take part in this study and answered a questionnaire regarding lifestyle, medical history, and other factors. Results Old age, current and former smoking, sedentary work, short sleep time, coronary artery stenosis, treatment with statins, medical history of cerebrovascular disease, medical history of angina pectoris, medical history of ischemic heart disease, and medical history of dyslipidemia were associated with higher odds ratios than the other factors examined, while the Japanese-style breakfast (e.g. boiled rice, miso soup, grilled fish) was associated with lower odds ratios. Conclusions In this study, smoking, sedentary work, short sleep time, and the Japanese-style breakfast were lifestyle factors related to coronary artery calcification. The lifestyle of Japanese people may be related to coronary calcification.

Background Left ventricular assist device (LVAD) mechanically unloads the left ventricle (LV). Theoretical analysis indicates that partial LVAD support (p-LVAD), where LV remains ejecting, reduces LV preload while increases afterload resulting from the elevation of total cardiac output and mean aortic pressure, and consequently does not markedly decrease myocardial oxygen consumption (MVO2). In contrast, total LVAD support (t-LVAD), where LV no longer ejects, markedly decreases LV preload volume and afterload pressure, thereby strikingly reduces MVO2. Since an imbalance in oxygen supply and demand is the fundamental pathophysiology of myocardial infarction (MI), we hypothesized that t-LVAD minimizes MVO2 and reduces infarct size in MI. The purpose of this study was to evaluate the differential impact of the support level of LVAD on MVO2 and infarct size in a canine model of ischemia-reperfusion. Methods In 5 normal mongrel dogs, we examined the impact of LVAD on MVO2 at 3 support levels: Control (no LVAD support), p-LVAD and t-LVAD. In another 16 dogs, ischemia was induced by occluding major branches of the left anterior descending coronary artery (90 min) followed by reperfusion (300 min). We activated LVAD from the beginning of ischemia until 300 min of reperfusion, and compared the infarct size among 3 different levels of LVAD support. Results t-LVAD markedly reduced MVO2 (% reduction against Control: -56 ± 9%, p

Although vagal nerve stimulation (VNS) in the acute phase of AMI has a powerful anti-ischemic effect, technical difficulties associated with VNS preclude its application under emergency clinical settings. Furthermore, how the acute phase VNS translates into the long term benefit remains unknown. In

Purpose: Although the augmented sympathetic nerve activity (SNA) is a salient feature of heart failure, while vagal nerve stimulation (VNS) benefits patients with heart failure. How the VNS impacts on SNA remains unknown. Since the vagal trunk has both efferent and afferent fibers, we hypothesized that the vagal afferent stimulation (AVNS) impacts on baroreflex control of SNA. Methods and results: In 6 anesthetized, ventilated rats, we controlled the pressure of isolated, bilateral carotid sinuses (CSP) and measured celiac SNA and arterial pressure (AP). Under a constant CSP at 100 mmHg, increasing the voltage of AVNS captured the vagal afferent nerves at 2-4 volts and dose dependently decreased SNA and AP. The averaged maximal inhibition of SNA were -27.3±5.3% (Fig. 1). To examine the impact of AVNS on the baroreflex system, we changed CSP stepwise and measured the response of SNA and AP with/without AVNS. AVNS reset the sigmoidal CSP-SNA relation (neural arc) downward, whereas unaffected the linear SNA-AP relation (peripheral arc) (Fig. 2). To evaluate the dynamic impacts of AVNS on SNA, we randomly stimulated AVNS with binary white noise sequences, and identified the transfer function from AVNS to SNA and that from SNA to AP. We also identified transfer function of native baroreflex from CSP to SNA and from SNA to AP. The transfer functions from AVNS to SNA strikingly resembled that from CSP to SNA. The transfer functions from SNA to AP were indistinguishable whether we perturbed CSP or AVNS indicating that they share the common central and peripheral neural mechanism. ![Figure][1] Conclusions: AVNS resets the baroreflex neural arc and induces sympathoinhibition just like the native baroreflex. The AVNS induced sympathoinhibition may in part attribute to the beneficial impacts of VNS on heart failure. [1]: pending:yes

Purpose: The pressure-volume area (PVA) of the left ventricle (LV) is tightly coupled with myocardial oxygen consumption/demand (MVO2). Theoretical analysis indicates that, the partial LVAD support (PARTIAL) where LV remains ejecting, reduces LV preload while increases afterload, and thus does not decrease much the PVA or MVO2. In contrast, the total LVAD support (TOTAL) where LV no longer ejects, markedly decreases LV volume, thereby MVO2. We hypothesized PARTIAL and TOTAL unloading would have major differences in the infract size in ischemia-reperfusion injury. Methods: We created ischemia by occluding major branches of the left anterior descending coronary artery for 90 min, reperfused for the following 300 min and assessed the infract size (normalized by the risk area). We allocated 12 anesthetized dogs into 3 groups, no support (CONT), PARTIAL (LV output=LVAD flow) and TOTAL (no LV output). Results: Mean arterial pressure (MAP) did not differ among 3 groups (CONT: 97±11, PARTIAL: 96±2.6 and TOTAL: 101±7.1 mmHg). In TOTAL, LV peak-systolic pressure (42±11 mmHg) was much lower than that of MAP confirming no LV ejection. LVAD significantly reduced the infarct size (CONT: 40±3.2, PARTIAL: 27.6±5.8, and TOTAL: 5.0±1.6%, p

available for 132 patients (58.1%). Patients were followed for a median of 774 days (IQ; 447.5, 1080). LVRR was defined as a decrease in indexed left ventricular systolic dimension of at least 15% and a 25% improvement in left ventricular ejection fraction (LVEF) at outpatient check-up compared with measurements at discharge. LVRR accomplishment within 400 days was defined as early-LVRR. The remaining LVRR patients were classified as late-LVRR. The patients had a mean age of 63.86615.12 years; 80.3% were male, and 72.0% had a non-ischemic etiology. LVRR was observed in 51 patients (38.6%). Overall, there were 53 events of death or heart failure hospitalization. Events in the LVRR and non-LVRR groups was 12 (23.5%) and 53 (50.6%), respectively (logrank test, p!0.001). LVRR was a predictor of favorable prognosis (HR, 2.85; p 5 0.007) and early-LVRR was associated with better prognosis compared with the late-LVRR group (log-rank test, p 5 0.004). Prognosis was improved in patients who achieved LVRR. Early response to treatment was a major advantage in terms of long-term prognosis.

Takamori Kakino, Tomohiro Nakayama, Hideo YamamotoDepartment of Cardiology and Radiology, Kyushu Kosei–Nenkin Hospital, Kitakyushi City, JapanAbstract: After coronary catheterization, fever sometimes occurs, usually transiently. We report a very rare case that suggests persistent high fever and systemic inflammation might be caused by periaortitis induced by coronary catheterization including percutaneous coronary intervention.Keywords: periaortitis, percutaneous coronary intervention, fever, computed tomography