Ischemic Left Ventricular Failure Research Articles

A CASE OF SNAKE BITE WITH UNUSUAL COMPLICATIONS AND REVIEW OF LITERATURE

Snakebites, including poisonous ones, are common occurrence in tropical countries and are endemic during summer months. However, snake bite remains a neglected public health problem in resource limited countries like India. The snake venom may cause local cytotoxicity, hemotoxicity, neurotoxicity and myotoxicity. Cardiac involvement is not usually encountered and has not been extensively discussed. It is however reflected in ECG changes, echocardiographic changes, raised cardiac enzymes and new unexplained cardiac events.We recently managed case of cobra envenomation who presented with features of cytotoxicity leading to extensive cellulitis, coagulopathy and neuroparalysis. He was managed with polyvalent anti-snake venom (ASV) administration and supportive treatment. He recovered from neuroparalysis and was successfully weaned off the ventilator. Three days later, he developed ischemic cerebral infarction and left ventricular failure (LVF). Electrocardiography showed fresh ST-T changes in anterior and inferior leads. Echocardiography revealed features of severe, left ventricular (LV) dysfunction, markedly reduced ejection fraction (LVEF 20-25%) and mid-basal to apical akinesia. The patients LVF was managed with diuretic and resolved over next 48 h. Repeat echo after three days showed marked improvement in LVEF to 50% and only mild hypokinesia of akinetic segments. The transient LVF and echo findings were suggestive of the diagnosis of stress (Takotsubo) cardiomyopathy. We report this case for its unusual complications and review the relevant literature.

P1718Veno-arterial ECMO versus Left Impella bleeding complications in cardiogenic shock patients on dual antiplatelet therapy

Abstract Background Selective groups of patients, presenting with INTERMACS-1 cardiogenic shock due to acute ischaemic heart failure, may benefit from mechanical circulatory support (MCS). Patients with biventricular failure, severe septic shock or oxygenation problems should be selected for VA-ECMO, although the left Impella-CP heart pump can be considered as a less invasive alternative in supporting predominantly left ventricular failure. Bleeding issues are a major concern in patients on MCS, especially in this group where triple anticoagulation therapy (unfractionated heparin (UFH) for prevention of pump thrombosis and dual antiplatelet therapy (DAPT) after coronary stenting) is necessitated. We aim to investigate the bleeding and transfusion rate in DAPT-patients on VA-ECMO versus Impella. Methods We report single center data for 51 VA-ECMO and 8 Impella patients between 2011 and 2019. Indication for MCS was acute ischaemic cardiogenic shock. Patient demographics, transfusions and reported/radiographically diagnosed bleeding (BARC-classification) complications were analyzed. All patients received UFH and low dose aspirin plus clopidogrel or ticagrelor. Impella flow was at least 2.5 L/min. Transfusion targets were Hb >7 g/dl, fibrinogen >100 mg/dl (or >150 mg/dl when active bleeding) and platelet count >50/fL. Results Impella patients were significantly older (VA-ECMO 52.8 vs. Impella 62.4; p=0.02) as compared to the VA-ECMO group. Anti-Xa-levels and length of the MCS-run (mean 7.9 VA-ECMO vs. 6.4 days Impella) were comparable in both groups. Occurrences of minor bleeds was comparable between both groups (mainly oozing from the insertion site in the ImpellaTM group 63% vs. VA-ECMO 72%; p>0.05) but major bleedings with BARC score of 3 or more were significantly lower in the Impella group (13% vs. VA-ECMO 65%; p=0.005). Platelet and red blood cell transfusions were significantly lower in the Impella group (0.1 units of platelets per day vs. 1.1 units of platelets per day on VA-ECMO; p=0.002 and 0.8 units of RBCs per day vs. 2.6 units of RBCs per day on VA-ECMO; p=0.02). Bleeding/transfusion VA-ECMO vs Impella Conclusions Bleeding is a frequent complication of MCS. However, in our cohort, triple anticoagulation in acute cardiogenic shock due to ischaemic left ventricle failure resulted in a lower major bleeding rate when support was given by the left Impella device as compared with VA-ECMO therapy group. As a result, platelet and red blood cell transfusions were lower in the Impella group. These findings are likely to be partly explained by the increased number and size of cannulas in VA-ECMO, as well as the increased risk of haemolysis and consumptive coagulopathy due to the complexity and extensive foreign body surface of the ECMO-circuit. We conclude that Impella support should be considered as a safer option than VA-ECMO with regards to bleeding in patients with ischaemic left ventricular failure who require DAPT and MCS as a bridge to recovery or other definitive therapy.

Rehabilitative Care of A Patient with IHD and LVF

Cardiac rehabilitation is the restoration of a person to an optimal state of function. Cardiovascular diseases are the major cause of death which kills almost 10 times more women than breast cancer and more deaths in women than men. In cardiac rehabilitation we need to understand that ischemic heart disease is a chronic disease. It will not be cured nor will it disappear by itself. Therefore basic changes in life style must be made to promote recovery and health. The nurse can play a major role in teaching health promoting behaviors to the person at risk for CAD. The nurse caring for the older adults with IHD must be aware of the physiologic changes that occur in the cardiovascular system. So it is important that nurses should be included in a cardiac rehabilitation program. As nurses we need to equip our population to identify the important risk factors like obesity, physical inactivity, stress and consumption of fatty foods to halt the progress of this deadly disease. Case studies are often more effective than brochures, because everyone loves stories. There is a saying, “A picture is worth a thousand words”. The following case study is chosen to illustrate the Rehabilitative care of Ischemic Heart Disease & Left ventricular failure.

Early and Rarely - A Unique Case of Calcification in Stage 2 Chronic Kidney Disease.

A 60-year-old male presented to the hospital with ischemic heart disease (IHD), unstable angina and acute left ventricular failure. The patient had a history of diabetes mellitus (DM) and hypertension for last 10 years. He was also found to have renal dysfunction for last four months (CKD stage 2). Patient was taken for diagnostic coronary angiography, after taking precautions to prevent contrast induced nephropathy (CIN). For coronary angiography, femoral route was navigated initially, but the wire did not cross the lesion, so radial route was opted for performing angiography. The coronary angiogram revealed extensive calcification of all coronary arteries. Left anterior descending (LAD) artery and left circumflex (LCX) artery showed insignificant disease but proximal mid right coronary artery (RCA) junction showed 80% stenosis [Table/Fig-1,​,2].2]. We also observed unusual ‘round magic ball’ like appearance of extensive aortic calcification. [Table/Fig-1]: Right coronary artery (RCA) calcification [Table/Fig-2]: Calcification of aorta, left main coronary artery (LMCA), left anterior descending (LAD) artery and left circumflex artery (LCX) The term ‘chalky arteries’ is no more a ‘rare’ term when, debating about chronic kidney disease. The aortic and vascular calcification is an active metamorphic process involving phenotypic change of vascular smooth muscle cells (VSMCs) into bone forming cells. A fusillade of various events like high phosphate environment, excess of calcium, high dose of active vitamin D therapy and increased expression of osteoblastic markers like Runx-2, alkaline phosphatase and osteocalcin causes mineralization of VSMCs [1]. After phenotypic change in VSMCs and production of bone matrix protein, the role of matrix vesicles and apoptotic bodies come into picture to concentrate calcium and phosphate in preparation for mineralization [2]. The voluminous literature demonstrates that prevalence of vascular calcification (VC) in CKD patients ranges from 47% to 92% [3]. But, the prevalence is mostly spotted in end stage renal disease (ESRD) [4]. A study reported the prevalence of coronary artery calcification (CAC) in young dialysis and peritoneal dialysis patients to be 80% [5]. The uniqueness of the case lies in the stage of chronic kidney disease, at which extensive calcification was observed. The aortic and coronary calcification in our case is seen in stage 2 of CKD, which is considered to be quite germinal for calcification. But still, in one of the pre-clinical studies, it was demonstrated that CKD stimulated vascular calcification begins early in the disease prior to even hyperphosphatemia [6]. The early stimulated calcification process worsens as the disease progresses [7]. This holds ground for our case, but the extensive calcification observed in all the coronary arteries [Table/Fig-1,2] at stage 2 CKD, directs us to look beyond the obvious. In a study by Yamada et al., multivariate logistic regression analysis was carried out, and it demonstrated that CKD in combination with DM, as well as hypertension in combination with CKD, were key relationships affecting the risk of arterial calcification, especially at the aortic arch and its orifices [8]. In our case, the patient has hypertension and DM for last 10 years. These co-morbid conditions may act as aggravating factors, along with CKD, in early predisposition of aortic and vascular calcification. The other typical presentation of the case is ‘round magic ball’ like appearance of aortic calcification [Table/Fig-2]. Usually, the calcification is present in the form of pigmentation adhered to the wall. But in our case, it is observed as round ball of calcified tissue in aorta. To the best of our knowledge, till now, none of the cases have reported such a distinct and startling ball-like calcification of aorta. In such cases, radial route should be preferred over femoral route. In our case, we initially tried femoral route, but the wire did not cross the calcific part of aorta at the junction of aortic arch and descending aorta. Aggressive manipulation in that part may lead to cerebral embolism. The radial route overcomes the junction of aortic arch & descending aorta, thereby reducing the chances of cerebral embolism. To sum up, the case provides insight into a different aspect, where calcification seems not only a threat to ESRD patients, but also as an early culprit. Aortic and vascular calcification in patients with CKD is a multifactorial interwining process, the pathologic mechanisms leading to such early calcification still remains to be elucidated.

Impact of levosimendan on right ventricular functions by using novel tissue Doppler derived indices in patients with ischaemic left ventricular failure

Right ventricular (RV) dysfunction complicates advanced left ventricular (LV) heart failure (HF) and contributes to a poor prognosis. Levosimendan is a positive inotropic agent improving cardiac contractility without increasing myocardial oxygen consumption in HF. To evaluate the effect of levosimendan therapy on RV systolic function, by using derived tissue Doppler imaging (TDI) in patients with ischaemic HF. The study consisted of 30 patients with HF who were admitted to our hospital due to new onset of decompensated HF, having LV ejection fraction < 40%, with functional status class III-IV, according to the New York Heart Association (NYHA). TDI-derived systolic velocities of tricuspid annulus (isovolumic myocardial acceleration [IVA], peak myocardial velocity during isovolumic contraction [IVV], peak systolic velocity during ejection period [Sa]) and diastolic indices (early [Ea] and late diastolic [Aa] velocities, Ea/Aa, E/Ea ratios and myocardial performance index [Tei index]) were measured. 72 hours after treatment, all measurements were re-evaluated. Considering TDI-derived systolic indices of the RV, IVA and IVV increased significantly, whereas Tei index decreased, after the therapy. Also, there was a significant decrease in serum levels of B-type natriuretic peptide. No significant change was observed in TDI derived diastolic indices of the RV. Levosimendan improves RV systolic function as expressed by TDI-derived parameters in patients with acutedecompensated HF.

End-diastolic flow reversal limits the efficacy of pediatric intra-aortic balloon pump counterpulsation

Counterpulsation with an intra-aortic balloon pump (IABP) has not achieved the same success or clinical use in pediatric patients as in adults. In a pediatric animal model, IABP efficacy was investigated to determine whether IABP timing with a high-fidelity blood pressure signal may improve counterpulsation therapy versus a low-fidelity signal. In Yorkshire piglets (n=19; weight, 13.0 ± 0.5 kg) with coronary ligation-induced acute ischemic left ventricular failure, pediatric IABPs (5 or 7 mL) were placed in the descending thoracic aorta. Inflation and deflation were timed with traditional criteria from low-fidelity (fluid-filled) and high-fidelity (micromanometer) blood pressure signals during 1:1 support. Aortic, carotid, and coronary hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption was calculated from coronary sinus and arterial blood samples. Left ventricular myocardial blood flow and end-organ blood flow were measured with microspheres. Despite significant suprasystolic diastolic augmentation and afterload reduction at heart rates of 105 ± 3 beats per minute, left ventricular myocardial blood flow, myocardial oxygen consumption, the myocardial oxygen supply/demand relationship, cardiac output, and end-organ blood flow did not change. Statistically significant end-diastolic coronary, carotid, and aortic flow reversal occurred with IABP deflation. Inflation and deflation timed with a high-fidelity versus low-fidelity signal did not attenuate systemic flow reversal or improve the myocardial oxygen supply/demand relationship. Systemic end-diastolic flow reversal limited counterpulsation efficacy in a pediatric model of acute left ventricular failure. Adjustment of IABP inflation and deflation timing with traditional criteria and a high-fidelity blood pressure waveform did not improve IABP efficacy or attenuate flow reversal. End-diastolic flow reversal may limit the efficacy of IABP counterpulsation therapy in pediatric patients with traditional timing criteria. Investigation of alternative deflation timing strategies is warranted.

Comparison of effect of rate control versus rhythm control on LV function in patients with AF and ischemic heart failure

The effect of rate control and rhythm control on left ventricular (LV) function in patients (pts) with atrial fibrillation (AF) and ischemic (LV) failure need to be delineated. The study was conducted on 48 pts with persistent AF of more than one week and less than one year duration and ischemic LV failure (EF < 50%). They were randomized into two groups matched in age and gender. Group 1: 24 pts submitted to rate control treatment. Group 2: 24 pts submitted to rhythm control treatment. Exclusion criteria: previous thromboembolism, left atrial (LA) or LA appendage thrombi, LA > 60 mm, intractable heart failure. Myocardial performance index (Tei index) was determined. Rate control: was achieved using digoxin, carvedilol, bisoprolol. Precardioversion TEE was done within 24 h of cardioversion. All pts received warfarin. Heart rate on admission and after one month follow up (mean): G1: 96 then 78. G2: 95 then 74. All improvement of LV function was statistically insignificant. NIHA class II, III and IV: G1: 100% then 66%, G2: 91% then 58%. The EF increased from 41% to 46% and 42% to 47%. Fractional shortening: G1 20 to 23; G2 20 to 23. Tei index improved in both groups: 1.4 and 0.96 to 1.27 and 0.74. LA diameter G1 50 mm to 52; G2 48 to 46. Both rate and rhythm control strategies are effective in controlling HR equally. There is no difference between both strategies in improvement in LV function after one month of therapy.

Intuitive visualization and quantification of intraventricular convection in acute ischemic left ventricular failure during early diastole using color Doppler-based echocardiographic vector flow mapping

The aim of this study was to make an intuitive visualization of intraventricular convection (IC) and quantification of intraventricular convection velocity (ICV) in acute ischemic left ventricular (LV) failure of open-chest canines during early diastole contrast to the baseline conditions using color Doppler-based echocardiographic vector flow mapping (VFM). The animal care committee approved this prospective study. In 6 anesthetized open-chest beagle models, the emergence time and the emergence sites of IC in the LV cavity during early diastole were visualized at the standard apical 3-chamber (AP3c) views with the VFM at baseline conditions and after coronary artery ligation. The global ICV and the ICV at the basal, middle and apical levels of LV at the AP3c views at T1, T2, T3, T4, and T5 between both states were compared respectively (T1: the beginning of LV rapid filling period; T2: the middle of LV rapid filling period; T3: the peak of LV rapid filling period; T4: the middle of period of reduced filling; T5: the end of early diastole.). Acute ischemic LV failure with a marked increase in LV end diastolic volume and LV minimal diastolic pressure was induced by coronary artery ligation. The IC appeared only during the period of reduced filling at baseline conditions, and limited to the basal level of LV cavity. But the IC appeared throughout all the early diastole, and was seen almost occupying whole LV cavity during ischemia. The peak of the global ICV for both states appeared at T4. The global ICV at the AP3c views in acute ischemic failure LV cavity increased than those of baseline conditions at the T1 (6.593 ± 0.834 cm(2)/s vs. 0.000 ± 0.000 cm(2)/s, P < 0.001), T2 (9.457 ± 0.852 cm(2)/s vs. 0.000 ± 0.000 cm(2)/s, P < 0.001), T3 (14.765 ± 1.791 cm(2)/s vs. 2.030 ± 0.502 cm(2)/s, P < 0.001), T4 (25.392 ± 4.640 cm(2)/s vs. 6.688 ± 1.343 cm(2)/s, P < 0.001), and T5 (15.890 ± 3.159 cm(2)/s vs. 2.518 ± 0.869 cm(2)/s, P < 0.001). And the ICV at the basal, middle and apical levels at AP3c views in acute ischemic failure LV cavity also increased than those of baseline conditions at the same phase of early diastole (P < 0.01), except for the ICV at the LV basal level at T1. VFM is a powerful tool for visualization IC and quantification of ICV on profiles of LV flow fields, which can give intriguing insights into the subtle, flow-associated LV fluid dynamics of normal and abnormal cardiac function. It will be of great practical importance to elucidate the accurate physiological and the pathophysiological significance of the IC in further studies, so as to determine whether the cardiac function can be precisely evaluated with IC related index, and to incorporate VFM into clinical routine practice in the future.

Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy

Although there is tremendous interest in stem cell (SC)-based therapies for cardiomyopathy caused by chronic myocardial infarction, many unanswered questions regarding the best approach remain. The TAC-HFT study is a phase I/II randomized, double-blind, placebo-controlled trial designed to address several of these questions, including the optimal cell type, delivery technique, and population. This trial compares autologous mesenchymal SCs (MSCs) and whole bone marrow mononuclear cells (BMCs). In addition, the study will use a novel helical catheter to deliver cells transendocardially. Although most trials have used intracoronary delivery, the optimal method is unknown and data suggest that the transendocardial approach may have important advantages. Several trials support the benefit of SCs in patients with chronic ischemic cardiomyopathy (ICMP), although the sample sizes have been small and the number of trials sparse. After a pilot phase of 8 patients, 60 patients with ICMP (left ventricular ejection fraction 15%-50%) will be randomized to group A (30 patients further randomized to receive MSC injection or placebo in a 2:1 fashion) or group B (30 patients further randomized to BMCs or placebo in a 2:1 fashion). All patients will undergo bone marrow aspiration and transendocardial injection of SCs or placebo. The primary and secondary objectives are, respectively, to demonstrate the safety and efficacy (determined primarily by cardiac magnetic resonance imaging) of BMCs and MSCs administered transendocardially in patients with ICMP.

Improved left ventricular unloading and circulatory support with synchronized pulsatile left ventricular assistance compared with continuous-flow left ventricular assistance in an acute porcine left ventricular failure model

Controversy exists regarding the optimal pumping method for left ventricular assist devices. The purpose of this investigation was to test the hypothesis that pulsatile left ventricular assist synchronized to the cardiac cycle provides superior left ventricular unloading and circulatory support compared with continuous-flow left ventricular assist devices at the same level of ventricular assist device flow. Seven male pigs were used to evaluate left ventricular assist device function using the TORVAD synchronized pulsatile-flow pump (Windmill Cardiovascular Systems, Inc, Austin, Tex) compared with the Bio-Medicus BPX-80 continuous-flow centrifugal pump (Medtronic, Inc, Minneapolis, Minn). Experiments were carried out under general anesthesia, and animals were instrumented via a median sternotomy. Hemodynamic measurements were obtained in the control state and with left ventricular assistance using the TORVAD and BPX-80 individually. Left ventricular failure was induced with suture ligation of the mid-left anterior descending coronary artery, and hemodynamic measurements were repeated. During left ventricular assist device support, mean aortic pressure and total cardiac output were higher and left atrial pressure was lower with pulsatile compared with continuous flow at the same ventricular assist device flow rate. During ischemic left ventricular failure, pulsatile left ventricular support resulted in higher total cardiac output (5.58± 1.58 vs 5.12± 1.19, P<.05), higher mean aortic pressure (67.8± 14 vs 60.2± 10, P<.05), and lower left atrial pressure (11.5± 3.5 vs 13.9± 6.0, P<.05) compared with continuous flow at the same left ventricular assist device flow rate. Synchronized, pulsatile left ventricular assistance produces superior left ventricular unloading and circulatory support compared with continuous-flow left ventricular assist at the same flow rates.

Coronary Artery Bypass for Heart Failure in Ischemic Cardiomyopathy: 17-Year Follow-Up

Coronary artery bypass grafting (CABG) has been safely extended to ischemic cardiomyopathy and heart failure, but outcome beyond 5 years remains poorly defined. We retrospectively analyzed 45 consecutive angina-free patients with ischemic left ventricular dysfunction (ejection fraction < or = 0.35) and heart failure (New York Heart Association functional class III to IV) who were selected for CABG between 1988 and 1995. Positron emission tomography was used for preoperative identification of myocardial viability. The 30-day mortality was 4.4%. At a median follow-up of 117 months (longest observation, 205 months), the probability of survival at 1, 5, 10, and 15 years after CABG was 93.3%, 84%, 65%, and 44%, respectively. At multivariable analysis, a left ventricular end-diastolic pressure (LVEDP) of 25 mm Hg or more predicted a threefold increase of the hazard of death (p = 0.02), whereas a LVEDP of 20 mm Hg or more correlated with the requirement of an intraaortic balloon pump perioperatively (p = 0.04). Other independent predictors of survival were age older than 70 years and peripheral vascular disease. Cardiac events accounted for 88% of late deaths, which were primarily related to sudden death or progressive heart failure. Most patients were in New York Heart Association functional class I to II at late follow-up. CABG alone yields good long-term outcome in selected angina-free patients with ischemic systolic dysfunction and advanced heart failure. However, associated diastolic impairment, reflected by elevated LVEDP, predicts reduced long-term survival despite myocardial viability.

Nitric oxide synthase inhibition impairs myocardial efficiency and ventriculo‐arterial matching in acute ischemic heart failure

The effect of nitric oxide (NO) manipulation in acute heart failure has not been sufficiently investigated. Therefore, we assessed the impact of NO-synthase (NOS) inhibition on left ventricular (LV) function and energetics as well as overall hemodynamics, in a porcine model of acute ischemic LV failure. Acute heart failure was induced by left coronary artery microembolization in fourteen anesthetized pigs. LV pressure-volume relationships and mechanical work (PVA) were assessed 30 min after stable heart failure, using pressure-conductance catheters. Myocardial oxygen consumption (MVO(2)) was determined from coronary flow and coronary arteriovenous oxygen difference. Microembolization led to a significant decrease in cardiac output, arterial pressure and LV systolic and diastolic performance. Animals were then randomized to a control group (n=7) or to receive 15 mg/kg N(omega)-Nitro-L-arginine-metyl ester (n=7), an inhibitor of NO synthase (NOS). Measurements 15 min later revealed that NOS inhibited animals had significantly reduced cardiac output (1.53+/-0.45 vs. 2.13+/-0.49 l/min, P=0.003) and stroke work (1054+/-461 vs. 1296+/-348 mmHg ml, P=0.03), and also displayed a significant increase in the slope of the MVO(2)-PVA relationship (2.57+/-0.53 vs. 1.92+/-0.15, P=0.008), i.e. an inefficient chemomechanical coupling. NOS inhibition did not alter contractility, diastolic function or arterial pressure, but afterload was significantly increased compared to controls (arterial elastance 6.03+/-1.48 vs. 2.74+/-0.34 mmHg/ml, P=0.009). Inhibition of NOS in experimental acute heart failure increased afterload without altering left ventricular systolic and diastolic function. Consequently, cardiac output was reduced. Furthermore, mechanoenergetic efficiency was severely impaired. NOS inhibition in acute heart failure and cardiogenic shock warrants further investigations.

Preserved myocardial energetics in acute ischemic left ventricular failure -- studies in an experimental pig model.

We hypothesised that acute ischemic left ventricular failure is characterised by depressed systolic and diastolic function combined with inefficiency in oxygen to mechanical work energy transfer. Eight anaesthetised pigs (32+/-3 kg) were employed in an in vivo open chest model. Intraventricular combined pressure and conductance catheters were used to generate continuous left ventricular pressure-volume relations. Myocardial oxygen consumption (MVO(2)) was determined from coronary flow and coronary arteriovenous oxygen difference. After baseline measurements, ischemia was induced by repeated left coronary injections of 50 microm polystyrene microspheres until stroke volume was reduced by 30%. Haemodynamic and biochemical measurements were repeated 30, 90 and 150 min after microembolisation. Coronary embolisation induced a significant reduction in stroke work (2749+/-504-1473+/-449 mmHg ml, P<0.05) at 30 min compared to baseline. Post-embolic contractility was reduced measured by the slope of the preload recruitable stroke work index (66.2+/-12.8-50.0+/-5.8 mmHg, P<0.05) and the slope of the curvilinearly fitted end-systolic pressure-volume relation in V(0) (7.1+/-2.2-4.9+/-2.2 mmHg/ml, P<0.05). The dP/dt(min) decreased (2076+/-291-1468+/-266 mmHg/s, P<0.05), but there was no significant change in diastolic stiffness or Tau. Following the 30 min measurements, there were only small changes in most indices. We found no change in myocardial oxygen consumption for basal metabolic processes or excitation-contraction coupling (unloaded MVO(2)), and there were no changes in conversion of oxygen to total mechanical work (MVO(2)-PVA slope). However, decreased mechanical efficiency (SW/MVO(2)) paralleled an increased ratio of arterial elastance to ventricular elastance. Coronary microembolisation in pigs induce a stable ischemic left ventricular failure characterised by reduced contractility and minimally impaired diastolic function. In this acute ischemic left ventricular failure, the main contributor to all over cardiovascular inefficiency is increased ratio of arterial- to ventricular elastance, a setting that impairs mechanical efficiency. However, efficiency of oxygen to total mechanical work transfer in the myocardium is unaltered. The mechanism behind this finding is elusive and warrants further investigation.

Development of Acute Ischemic Heart Failure in Sheep

The goal of the present study was to develop a large animal model of acute ischemic left ventricular heart failure (LVHF) that can be used to assess the influence of the PUCA pump on the heart and circulatory system under realistic conditions. We tested the hypothesis that mild stenosis of the coronary artery in combination with mild ventricular pacing induces an acute heart failure condition, whereas the separate phenomena themselves do not lead to impaired heart function. Mean aortic pressure (AoP), left ventricular end-diastolic pressure (LVEDP), stroke volume (SV) and myocardial systolic shortening (MSS) were compared 30 minutes after a pacemaker (PM) induced tachycardia in anaesthetized sheep (n=3) without and with +/- 50% stenosis of the proximal LCx. All parameters measured restored to basic levels when stenosis was absent. When the LCx was partially occluded, mild PM-induced tachycardia resulted in decreased AoP (P=0.045) as well as in decreased SV (P=0.048); the LVEDP remained high (P=0.002). Also the recovery of MSS was impaired when stenosis was present (P=0. 002). These values indicate that acute heart failure conditions were present. The technique used proved to be safe and allowed fine-tuning of the demand ischemia by adapting heart frequency to the required heart failure conditions. The model can be used to study the effect of LV mechanical support during acute heart failure conditions.

Mechanisms of retarded apical filling in acute ischemic left ventricular failure.

We examined the hypothesis that retardation of apical filling as measured by color M-mode Doppler echocardiography in the diseased left ventricle (LV) reflects a decrease in the intraventricular mitral-to-apical pressure gradient. In 9 open-chest anesthetized dogs, micromanometers were placed near the mitral tip and in the apical region. From the color M-mode Doppler images, the time delay (TD) between peak velocity at the mitral tip and the apical region was determined as an index of LV flow propagation. Acute ischemic LV failure was induced by coronary microembolization. Induction of ischemia caused a marked increase in LV end-diastolic pressure and a decrease in LV ejection fraction. The time constant of LV isovolumic apical pressure decay (tau) increased from 31+/-8 to 49+/-16 ms (P<0.001). The peak early diastolic mitral-to-apical pressure gradient (DeltaPLVmitral-apex) decreased from 1.9+/-0.9 to 0.7+/-0.5 mm Hg (P<0.01), and TD increased from 5+/-3 to 57+/-26 ms (P<0.001). The slowing of flow propagation was limited to the apical portion of the LV cavity. The TD correlated with DeltaPLVmitral-apex (r=-0.94, P<0.01) and with tau (r=0.92, P<0.01). Before ischemia, the mitral-to-apical flow propagation velocity far exceeded the velocity of the individual blood cells, whereas during ischemia, flow propagation velocity approximated the blood velocity. Retardation of apical filling in acute ischemic failure was attributed to a decrease in the mitral-to-apical driving pressure, reflecting slowing of LV relaxation. The slowing of flow propagation appeared to represent a shift in apical filling from a pattern of column motion to a pattern dominated by convection.

The Effects of Cilazapril on Left Ventricular Remodeling after Coronary Intervention in Patients with Ischemic Heart Failure

Background and Objectives:Angiotensin converting enzyme inhibitor (ACEI) is known to be effective in the prevention of left ventricular failure (LVF) after acute myocardial infarction. The aim of this study was to investigate the efficacy of an ACEI, Cilazapril, on left ventricular remodeling in patients with ischemic LVF, who underwent coronary interventions. Materials and Methods:Cilazapril, 2.5-5.0 mg per day was administered 12 weeks after coronary interventions in 25 patients (18 M, 7 F, 61.5±9 years) with impaired LV function (ejection fraction≤50%). Fifteen patients (9 M, 6 F, 59.4±7 years) without ACEI were compared by clinical examinations, blood chemistry, electrocardiogram and echocardiogram with Cilzapril group at 2, 4, 8 and 12 weeks after intervention. Results:Blood pressure and heart rate were not changed after Cilazapril. LV end-diastolic volume (LVEDV) decreased from 153.1±38.7 to 135.6±25.5 ml and end-systolic volume from 84.9±34.7 to 72.6±25.1 ml after 12-week Cilazapril p=0.003, p=0.001. Ejection fraction (EF) was increased from 44.4±3.2 to 52.4± 2.8% after 12 weeks of Cilazapril p=0.034. In control group, LVEDV was changed from 152.7±44.6 to 143.6± 28.7 ml, which failed to show significant reduction. Side effects of Cilazapril were 3 dry cough (3/25, 12%) and 1 facial edema, 1 hypotension and 1 dizziness. Conclusion:Cilazapril is a beneficial adjunctive therapeutic agent in patients with ischemic left ventricular failure for the prevention of ventricular dilatation, especially after coronary intervention. (Korean Circulation J 1998;28(12):1964-1972)

Cardiac secretion of atrial and brain natriuretic peptides in acuteischaemic heart failure in pigs: effect of angiotensin II receptor antagonism

In a model of acute ischaemic left ventricular failure in pigs, we compared the plasma levels and cardiac secretion of the three atrial peptides, atrial natriuretic factor (ANF), N-terminal proatrial natriuretic factor (N-terminal proANF) and brain natriuretic peptide (BNP). Acute ischaemic left ventricular failure was induced by embolization of the left coronary artery with plastic microspheres. Thereafter, treatment was given by an intravenous injection of the angiotensin II receptor (AT1) antagonist losartan. Effects of failure induction and treatment were documented by measurement of haemodynamic parameters and plasma concentrations of catecholamines, plasma renin activity, angiotensin II and aldosterone. Acute left ventricular failure was accompanied by significant increases in cardiac secretion and plasma levels of all three atrial peptides, which was considerably more pronounced for ANF and N-terminal proANF than for BNP. Treatment with losartan resulted in significant decreases in plasma ANF and N-terminal proANF, whereas BNP did not change. These findings indicate that ANF and N-terminal proANF may be better suited than BNP as markers of cardiac preload during the development and treatment of acute heart failure.

Effects of failure of the right side of the heart and increased pulmonary resistance on mechanical circulatory support with use of the miniaturized HIA-VAD displacement pump system

This experimental study was designed to assess the influence of failure of the right side of the heart or pulmonary hypertension, or both, on the performance of a novel miniaturized left ventricular assist device. In small-sized dogs ( n = 50) ischemic global left ventricular failure was induced and support was provided by the HIA-VAD displacement pump (stroke volume 10 or 25 ml) installed as a left ventricular assist device. In three groups of animals ( n = 10 each) pulmonary hypertension was created before induction of global left ventricular failure. During left ventricular assist device support temporary ischemic failure of the right side of the heart was induced in four groups of animals ( n = 10 each). In the group subjected to left ventricular failure, support with the left ventricular assist device, and right ventricular failure during left ventricular assist, left atrial pressure and cardiac index were significantly lower than in the group subjected to left ventricular failure and left ventricular assist alone (2 ± 6 versus 11 ± 6 mm Hg and 1.6 ± 0.4 versus 1.0 ± 0.4 L/(min/m 2 ), respectively, p < 0.05). In the group subjected to pulmonary hypertension, left ventricular failure, and left ventricular support, left atrial pressure dropped to values near zero but cardiac index remained unaltered as compared with results with the same regimen without pulmonary hypertension. However, when right ventricular failure was added (that is, pulmonary hypertension, left ventricular failure, left ventricular support, and right ventricular failure during support with the left ventricular assist device) left atrial pressure dropped to negative values ( p < 0.05) and cardiac index progressively deteriorated. When, in an additional group of dogs, biventricular support was installed in the latter regimen, circulation was initially well supported but oxygenation deteriorated in 60% of cases. We conclude that (1) adequate right ventricular function was indispensable during support with the left ventricular assist device, (2) the combination of pulmonary hypertension and right ventricular failure led to the “low left ventricular assist device output syndrome,” and (3) biventricular mechanical support in the presence of pulmonary hypertension may be complicated by the alveolar leakage syndrome. (J T horac C ardiovasc S urg 1996;112:484-93)

Editorial on “coronary artery bypass grafting in patients with an ejection fraction of twenty percent or less”

Editorial on “coronary artery bypass grafting in patients with an ejection fraction of twenty percent or less”

Dobutamine echocardiography and thallium-201 imaging predict functional improvement after revascularisation in severe ischaemic left ventricular dysfunction.

To evaluate the concordance between thallium-201 uptake and echocardiographic wall thickening, which are both indicators of potentially reversible myocardial dysfunction, in patients with chronic ischaemic left ventricular failure and to assess their relative contribution to predicting improvement in regional function after revascularisation in a subgroup. 45 patients with chronic ischaemic left ventricular dysfunction (mean (SD) ejection fraction 25 (8)%) underwent echocardiography before and after dobutamine infusion (10 micrograms/kg/min). Of these, 22 patients underwent rest echocardiography at a mean (SD) of 9 (1) weeks after revascularisation. 201Tl imaging was performed during dobutamine echocardiography and at rest, 1, and 4 h after treatment with sublingual glyceryl trinitrate on two separate days. Potentially reversible dysfunction was thought to be present when a myocardial segment contained a Tl score of > or = 3 (ascending score 1-4), or showed improved wall thickening of a dysynergic segment during dobutamine stimulation. Of the 201Tl protocols, the redistribution scan 1 h after treatment with glyceryl trinitrate best demonstrated myocardial viability. Concordance between 201Tl and dobutamine induced wall thickening was 82% (kappa = 0.59) for detecting potentially reversible myocardial dysfunction before revascularisation (n = 45). Regional function improved in 18 of 22 patients after revascularisation. There were 168 dysynergic segments before intervention. The sensitivity of echocardiography and 201Tl imaging for detecting "recoverable" or viable segments after revascularisation was 87% and 92% respectively and specificity was 82% and 78% respectively (P = NS). Dobutamine echocardiography and 201Tl imaging may be used to predict mechanical improvement in dysynergic segments after revascularisation in patients with chronic ischaemic left ventricular dysfunction.