Unloading Therapy Research Articles

Left ventricular unloading therapy using Impella 5.5 after emergency surgery for acute myocardial infarction mechanical complication: a case report

BackgroundFollowing an acute myocardial infarction (AMI), surgery for left ventricular free wall rupture (LVFWR) and ventricular septal rupture (VSR) has a high in-hospital mortality rate, which has not improved significantly over time. Unloading the LV is critical to preventing excessive stress on the repair site and avoiding problems such as bleeding, leaks, patch dehiscence, and recurrence of LVFWR and VSR because the tissue is so fragile. We present two cases of patients who used Impella 5.5 for LV unloading following emergency surgery for AMI mechanical complications.Case presentationA 76-year-old male STEMI patient underwent fibrinolysis of the distal right coronary artery. Three days later, he passed out and went into shock. Echocardiography revealed a cardiac tamponade. We found an oozing-type LVFWR on the posterolateral wall and treated it with a non-suture technique using TachoSil. Before the patient was taken off CPB, Impella 5.5 was inserted into the LV via a 10 mm synthetic graft connected to the right axillary artery. We kept the flow rate above 4.0 to 4.5 L/min until POD 3 to reduce LV wall tension while minimizing pulsatility. On POD 6, we weaned the patient from Impella 5.5. A postoperative cardiac CT scan showed no contrast leakage from the LV. However, a cerebral hemorrhage on POD 4 during heparin administration complicated his hospitalization. Case 2: A diagnosis of cardiogenic shock caused by STEMI occurred in an 84-year-old male patient, who underwent PCI of the LAD with IABP support. Three days after PCI, echocardiography revealed VSR, and the patient underwent emergency VSR repair with two separate patches and BioGlue applied to the suture line between them. Before weaning from CPB, we implanted Impella 5.5 in the LV and added venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for right heart failure. The postoperative echocardiography revealed no residual shunt.ConclusionsPatients undergoing emergency surgery for mechanical complications of AMI may find Impella 5.5 to be an effective tool for LV unloading. The use of VA-ECMO in conjunction with Impella may be an effective strategy for managing VSR associated with concurrent right-sided heart failure.

Priority choice of topical antibacterial drugs in the commonly accepted paradigm of acute rhinosinusitis treatment

Introduction. In the complex therapy of acute rhinosinusitis, topical drugs with different mechanisms of action and influence on the main links in the pathogenesis of acute infectious lesions of the mucous membrane of the paranasal sinuses are widely used. Local drugs with antibacterial, as well as mucolytic and vasoconstrictor effects do not inhibit mucociliary clearance, have a convenient release form and ensure dosing accuracy with each use.Aim. Evaluation of the clinical effectiveness of the use in complex therapy of a topical antibiotic of the aminoglycoside group in combination with a drug having vasoconstrictive and mucolytic effects of domestic production in the treatment of acute bacterial rhinosinusitis.Materials and methods. The study involved 30 patients with a verified diagnosis of acute bacterial rhinosinusitis of moderate severity aged 18 to 68 years, who were divided into two groups. Patients of the first group (n = 15), in addition to complex treatment (antibacterial, antihistamine and unloading therapy, anti-inflammatory and puncture treatment), used a drug with a bactericidal effect from the group of aminoglycosides (Tramicent). Patients of the second group (n = 15) supplemented the same treatment with a drug with mucolytic and vasoconstrictive action (Rhinostein®). The effectiveness of therapy was evaluated based on the results of three visits to the doctor within two weeks.Results. The positive dynamics of the subjective and objective status of patients in both study groups was noted. By the 3rd visit (10–14 days), the severity of clinical manifestations in patients who used two drugs Tramicent and Rhinostein® as additional therapy was 2 times lower than at the first visit compared with the group of patients who used only Tramicent as additional therapy. The absence of complaints after treatment in the 2nd group was noted by 15% of the examined, in the 1st – 10%.Conclusions. Topical drug from the group of aminoglycosides containing the active substance framycetin sulfate (Tramicent) in the form of a spray is a safe and effective remedy in the complex therapy of bacterial rhinosinusitis, and its use in combination with the drug mucolytic and vasoconstrictive action (Rhinostein®) significantly reduces the duration of treatment and improves the quality of life of patients.

Left ventricular afterload reduction by transcatheter aortic valve implantation acutely alleviates right ventricular pacing-induced left ventricular dysfunction in patients with aortic stenosis

Abstract Introduction In patients with left bundle branch block (LBBB) cardiac function has been found to be particularly sensitive to alterations in left ventricular (LV) afterload. Nevertheless, whether the detrimental hemodynamic effect of right ventricular pacing (RVP)-induced electromechanical dyssynchrony on LV function is also associated with afterload dependency, has not been investigated yet. Purpose Hence, in the current study we sought to examine the acute effect of RVP on LV function in patients with aortic stenosis (AS) before (with elevated afterload) and after (without elevated afterload) transcatheter aortic valve implantation (TAVI). Methods Patients with a previously implanted permanent pacemaker (PM) and significant AS referred for TAVI at our heart and vascular center university were screened for this observational study. Only those patients who had an intrinsic, regular, narrow QRS or right bundle branch block (RBBB) morphology rhythm were included. From 2022 March to 2023 February, nine patients with a DDD PM (with sick sinus syndrome and maintained AV conduction) and four patients with a VVI PM (with atrial fibrillation and complete AV block but stable junctional escape rhythm) were enrolled. Following TAVI, four patients were excluded due to the development of new-onset persistent LBBB. Transthoracic conventional and advanced echocardiography and non-invasive blood pressure monitoring were performed immediately before TAVI and on the second postoperative day. The measurements were carried out during intrinsic QRS rhythm and during frequency-matched RVP as well. Global longitudinal strain was determined by speckle-tracking echocardiography, then using LV pressure curves estimated from systolic blood pressure and mean aortic gradient, global myocardial work index (GMWI) was calculated to assess LV contractility. Results Mean aortic gradient was decreased after TAVI (40.2±3.6 vs. 6.7±1.3mmHg before vs. after TAVI, P<0.001) indicating successful reduction of LV afterload. Compared to the intrinsic QRS rhythm, RVP decreased GMWI before TAVI (GMWI: 1967±206 vs. 1240±174mmHg% intrinsic QRS vs. RVP, P<0.001) and after TAVI (GMWI: 1399±149 vs. 1020±121mmHg% intrinsic QRS vs. RVP, P=0.019) as well. Nevertheless, the extent of RVP-induced LV contractility impairment (expressed as ΔGMWI) was significantly alleviated after pressure unloading therapy (ΔGMWI: -37.1±6.6 vs. -24.5±7.8% before TAVI vs. after TAVI, P=0.024). Conclusion Our preliminary results indicate that RVP-induced LV dysfunction is afterload dependent. Hence, in patients with AS and a high percentage of RVP, TAVI might entail substantial functional improvement.

P164 PERCUTANEOUS LEFT STELLATE GANGLION BLOCK IN REFRACTORY LEFT ATRIAL TACHYCARDIA

Abstract Percutaneous left stellate ganglion block (PLSGB) has been recently implemented for the acute treatment of refractory ventricular arrhythmias (VAs). The beneficial effect on supraventricular arrhythmias susceptibility and their ventricular response is well characterized in animal models, less so in humans. Available data suggest a significant prolongation of atrial refractory period, a reduction in inducibility and duration of atrial fibrillation and of all spontaneous intra– and postoperative atrial arrhythmias after thoracic and cardiac surgery. Here we describe a case of PLSGB for focal atrial tachycardia (AT). Case: we present a 68–year–old men with hypertension, obesity, OSAS and previous anterior myocardial infarction in the setting of a trivessel coronary disease, treated with PCI and complicated by apical aneurysm, with a LVEF of 38% and a moderate mitral and aortic regurgitation. He was on chronic antiarrhythmic therapy with bisoprolol 1.25 mg and ranolazine. He presented in the ED due to palpitations, pre–syncopal episodes, and worsening dyspnea. The ECG showed very frequent, self–limiting episodes of AT with a 1:1 atrioventricular (AV) conduction and a variable heart rate (HR) between 100 and 160 bpm, alternating with sinus rhythm at 45–50 bpm, sometimes conducted with aberrancy. Isolated and repetitive premature ventricular beats (PVB, maximum 8 beats) were also documented. Amiodarone, lidocaine, and intravenous unloading therapy were tried, without benefit. Coronary angiography was negative. PLSGB with an ultrasound–guided lateral approach (local bolus of lidocaine 100 mg+ropivacaine 20 mg) was performed, without complications, inducing palpebral ptosis. Over the next 15 hours we observed the disappearance of non–sustained VAs, the reduction of PVBs, and a progressive reduction of AT burden, of mean hourly HR (from 84 to 50 bpm, –40%) and of mean HR during AT (from 158 to 84 bpm, –47%, with AV 1:1 conduction). The patient subsequently underwent ablation of an extra systolic focus found near the ostium of the right inferior pulmonary vein, with no recurrences after 18 months. Conclusions This case highlights the potential efficacy of PLSGB in the acute treatment of supraventricular arrhythmias refractory to medical therapy. Prospective studies will help us to identify the extent, time of onset, and duration of its benefit depending on the type and mechanism of the underlying arrhythmia and the clinical characteristics of the patient.

Results of unloading therapy of acute infectious rhinitis with 0.1% xylometazoline

Introduction. Acute infectious rhinitis refers to the frequent causes of discharge therapy with nasal decongestants. The aim to analyze the clinical features of unloading therapy of acute infectious rhinitis with 0.1 % xylometazoline according to the materials of the research centers of Novosibirsk and Yekaterinburg. Materials and methods. In the research centers of Novosibirsk and Yekaterinburg, patients with acute infectious rhinitis were observed. Intranasal therapy in the study groups (group 1) and in the comparison groups (group 2) was carried out with 0.1 % xylometazoline spray for 7 days. Group 2 additionally received silver preparation intranasally. The need for decongestant and the state of mucociliary transport (MCT) were evaluated. Results and discussion. Initially, patients with normal MCT rate at 1 visit in Novosibirsk accounted for 20.8 % in group 1 and 34.78 % in group 2; in Yekaterinburg – 29.17 % of patients in group 1 and 25% of patients in group 2. In the study groups, 54.2 % of patients in Novosibirsk and 100 % in Yekaterinburg used decongestant on day 5; in the comparison groups – 41.7% in Novosibirsk; 83.3% of patients in Yekaterinburg. On day 5, the volumetric air flow velocity was determined to be more than 900 cm3/s in all patients. Decongestant was used for more than 7 days by 40.35 % of patients in the first groups and 12.45 % of patients in the second groups. Inhibition of MCT on the 14 th day of follow-up, detected in two research centers, amounted to 5.26 % of patients. Conclusions. On the 5th day of unloading therapy, nasal breathing is objectively free. Intranasal antiseptic therapy reduces the probability of using decongestant for more than 7 days by 27.9 %. Inhibition of MCT when using 0.1 % xylometazoline should be attributed to frequent reactions.

Sex similarities and differences in the reverse and anti-remodeling effect of pressure unloading therapy in a rat model of aortic banding and debanding.

Investigating the effect of sex on pressure unloading therapy in a clinical scenario is limited by several nonstandardized factors. Hence, we sought to study sex-related similarities and differences under laboratory conditions. Pressure overload was induced in male and female rats by aortic banding (AB) for 6 and 12 wk. Age-matched sham-operated animals served as controls. Pressure unloading was performed by aortic debanding at week 6. Different aspects of myocardial remodeling were characterized by echocardiography, pressure-volume analysis, histology, qRT-PCR, and explorative proteomics. Hypertrophy, increased fetal gene expression, interstitial fibrosis, and prolonged active relaxation were noted in the AB groups at week 6 in both sexes. However, decompensation of systolic function and further deterioration of diastolic function only occurred in male AB rats at week 12. AB induced similar proteomic alterations in both sexes at week 6, whereas characteristic differences were found at week 12. After debanding, regression of hypertrophy and recovery of diastolic function took place to a similar extent in both sexes. Nevertheless, fibrosis, transcription of β-myosin-to-α-myosin heavy chain ratio, and myocardial proteomic alterations were reduced to a greater degree in females than in males. Debanding exposed anti-remodeling properties in both sexes and prevented the functional decline in males. Female sex is associated with greater reversibility of fibrosis, fetal gene expression, and proteomic alterations. Nevertheless, pressure unloading exposes a more pronounced anti-remodeling effect on the functional level in males, which is attributed to the more progressive functional deterioration in AB animals.NEW & NOTEWORTHY The present study is the first to assess the role of sex on pressure unloading-induced reverse and anti-remodeling in a rat model of aortic banding and debanding. Our data indicate that female sex is associated with a greater reversibility of fibrosis, fetal gene expression, and proteomic alterations compared with males. Nevertheless, pressure unloading exposes more anti-remodeling effect on the functional level in males, which is attributed to the more rapid functional deterioration in aortic-banded animals.

Single-centre experience with the Impella CP, in patients with cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: None. Background Short-term percutaneous mechanical circulatory support devices are increasingly used in cardiogenic shock. The choice between Impella or extra-corporeal membrane oxygenation (ECMO) is still a matter of concern. The purpose of this work was to identify the characteristics and clinical outcomes of Impella CP in patients with cardiogenic shock in a real world setting. Methods A retrospective single center study was performed on all cardiogenic shock patients that were treated with Impella CP from January 01th 2020 to April 30th 2021, the primary outcome was 30-day mortality. Secondary endpoint was the occurrence of device-related complications (limb ischemia, access site-related bleeding or dissection, access site-related infection). Results We identified 16 patients with cardiogenic shock who underwent placement of an Impella CP device. 8 patients (50%) underwent support in the setting of previously known chronic heart failure and acute decompensation, 5 patients (31.2%) for the assistance of a recent acute myocardial infarction, 2 (12.5%) for high-risk PCI and one case (6.25%) of hemodynamic support for an acute rejection following heart transplantation. In 10 cases (62.5%) the main indication was bridge to decision. The combination of Impella and ECMO (ECPELLA) as a unloading therapy was used in 7 patients (43.7%). The 30-day mortality was 37.5%. There were three vascular complications (18.7%) two dissections and one vascular occlusion, solved with good final results. Conclusions The application of the Impella CP is feasible in profound cardiogenic shock in multiple scenarios with an acceptable rate of complications. More data is needed to extend and standardize its use.

Left ventricular unloading during extracorporeal life support for myocardial infarction with cardiogenic shock: surgical venting versus Impella device.

Patients in cardiogenic shock supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO) may experience severe complications from reduced left ventricular (LV) unloading and increased cardiac afterload. These effects are usually modified by adding a percutaneous direct Impella vent or surgical LV vent on top of VA-ECMO in selected patients. However, direct comparisons between 2 LV unloading strategies in patients with cardiogenic shock due to myocardial infarction are lacking. Therefore, we sought to investigate the impact of these 2 different approaches. We enrolled 112 patients treated with an Impella or surgical LV vent during VA-ECMO support between January 2014 and February 2020. The primary endpoint was 30-day mortality. Secondary endpoints included rates of myocardial recovery or transition to durable mechanical circulatory support. Additionally, we assessed adverse events such as peripheral ischaemic complications requiring intervention, sepsis and ischaemic stroke. At 30 days, 38 patients in the Impella group (54%) and 26 patients in the surgical LV vent group (63%) had died (relative risk with Impella 0.78, 95% confidence interval 0.47-1.30; P = 0.35). Impella group and the surgical LV vent group differed significantly with respect to the secondary end points including rates of myocardial recovery (24% and 7%, respectively; P = 0.022) and rates of durable mechanical circulatory support (17% and 42%, P = 0.012). Complication rates were not statistically different between the 2 groups. The use of Impella device as therapeutic unloading therapy during VA-ECMO did not significantly reduce 30-day mortality compared to surgical LV vent in patients with cardiogenic shock due to acute myocardial infarction.

Дистракционная артропластика голеностопного сустава с использованием аппарата Илизарова и артроскопической техники: первый клинический опыт

We report a clinical case of a 27-year-old patient with posttraumatic painful ankle arthritis following sport injury treated with combined methods. The patient underwent ankle distraction arthroplasty with original Ilizarov apparatus and arthroscopic diagnosis and treatment of the ankle injury followed by the joint unloading and exercise therapy with frame on performed for 6 weeks at the Kurgan Ilizarov Center. The patient could improve pain relief and function at a long term following comprehensive treatment including surgical intervention, a course of physical procedures and exercise therapy. The combined technique can be used as an alternative treatment for patients with posttraumatic ankle arthritis.

Актуальность ситуационного использования назальных деконгестантов в современной клинической практике

Nasal decongestants (ND) are representatives of the pharmacological group of α-adrenomimetics and are widely used in clinical practice. These drugs are successfully used as symptomatic therapy of acute rhinosinusitis (AR), as well as as part of the complex therapy of acute otitis during unloading therapy for the auditory tube. The use of ND is necessary before conducting an endoscopic examination of the nasal cavity, for a better assessment of the state of the ostiomeatal complex, the olfactory cleft, as well as differential diagnosis of various forms of rhinitis and dysosmia. ND are indispensable in the prevention of complications of AR, such as acute eustachiitis, exudative otitis media and acute otitis media. Also, these drugs are used in the prevention of the development of aerotitis and ear barotrauma. The most commonly used nasal medications of medium and long duration of action, such as xylometazoline and oxymetazoline. This article presents clinical studies demonstrating the high efficacy and safety of these drugs as part of the treatment of AR. It is shown that oxymetazoline and xylometazoline are well tolerated by patients with a minimum number of adverse events. Modern representatives of ND are such drugs as Otrivin express 0.05% with the aroma of menthol, the main active ingredient of which is oxymetazoline, Otrivin 0.1% Moisturizing formula and Otrivin 0.1% with menthol and eucalyptus, which includes xylometazoline as the main active ingredient. These drugs have confirmed their effectiveness and safety in a large number of clinical studies and can be recommended as local vasoconstrictors.

Effect of ultrasonic cavitation on pro-inflammatory cytokine profile in complex therapy of patients with acute rhinosinusitis and exacerbation of chronic suppurative otitis media

Patients with exacerbated chronic suppurative otitis media occurring in subjects with acute rhinosinusitis often consulted by ENT spacialists. A literature review has shown that much attention is paid to improving conservative therapy for such patients, and non-drug techniques remain applied rarely. In this context, based on a detailed study of biophysical characteristics, an opportunity of using low-frequency ultrasonic cavitation in combination therapy to increase local immunological resistance of mucous membranes in ENT organ cavities is justified. The aim of the study was to increase clinical therapeutic effectiveness of acute rhinosinusitis and exacerbated chronic suppurative otitis media based on examining timeframe necessary for normalization of pro-inflammatory cytokine profile after using low-frequency ultrasonic cavitation in combination therapy. 63 patients were enrolled to the study. The control group (n = 15) consisted of healthy volunteers, whereas main group had 48 patients with acute rhinosinusitis and exacerbated chronic suppurative otitis media, subdivided into 2 subgroups: subgroup 1 (n = 20) – patients receiving conventional treatment methods (elimination, unloading, local and systemic antibacterial therapy, puncture and anti-inflammatory treatment), subgroup 2 (n = 28) – patients underwent low-frequency ultrasonic cavitation (frequency 29 kHz, amplitude 25 μm) in combination therapy. Washouts from the surface mucous membranes of nasal cavity and nasopharynx were examined for level of IL-1β, IL-2, IL-8, IL-10, TNFα, IFNγ levels before treatment, at day 2, 7, 10 days and in one month after treatment. Application of low-frequency ultrasonic cavitation in combination therapy in patients with acute rhinosinusitis associated with exacerbated chronic suppurative otitis media is accompanied by early recovery of balance in pro-inflammatory cytokines comparewd with conventional treatment methods. Data analysis showed that positive and satisfactory treatment result was achieved in 11 (56.2%) and 22 (78.2%) as well as 7 (36.2%) and 6 (21.8%) patients from subgroup 1 and 2, respectively. In two patients from subgroup 1 the result was noted as unsatisfactory. Early recovery in balance of pro-inflammatory cytokines, improvement of clinical results and shortened treatment duration were observed after using low-frequency ultrasonic cavitation in combination therapy of patients with acute rhinosinusitis and exacerbated chronic purulent otitis. The data obtained may serve to justify introduction of low-frequency ultrasonic cavitation into combination conservative therapy of infected nasal and middle ear cavities as an effective and non-invasive approach.

Outcome of Right Ventricular Primary Graft Dysfunction after Heart Transplantation

Primary graft dysfunction (PGD) is observed in approximately 7% of all heart transplant (HTx) patients (pts). According to the International Society for Heart and Lung Transplantation (ISHLT), a new PGD scale includes left ventricular (PGD-LV), or right ventricular (PGD-RV). PGD-LV when severe is noted to have increased mortality. PGD-RV has been described as hemodynamics with RAP >15 mmHg, PCWP <15 mmHg, CI < 2.0 L/min/m2, or need for RV temporary support. PGD-RV has not been well studied. Between Dec 2013 and Dec 2018, we assessed 13 HTx pts who developed PGD-RV within 24 hours after HTx and compared them to pts without PGD. Endpoints included 1-year survival, need for temporary kidney dialysis, need for RV unloading with sildenafil, first year rejection including any treated rejection (ATR), 1-year freedom from cardiac allograft vasculopathy (CAV), and 1-year freedom from non-fatal major adverse cardiac events (NF-MACE, defined as myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke). Pts with PGD-RV compared to pts without PGD had similar 1-year survival, freedom from CAV, freedom from NF-MACE, and rejection. 90% of pts with PGD-RV required RV unloading therapy which may have affected outcome. There was a trend for a lower freedom from temporary kidney dialysis in the PGD-RV group. PGD-RV after HTx appears to have acceptable outcome with good recovery. RV unloading therapy may be helpful. However, there was an associated increased need for temporary kidney dialysis within the first year after HTx. Larger numbers are warranted to confirm these findings.

GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload.

Chronic blood transfusions in patients with sickle cell anemia (SCA) cause iron overload, which occurs with a degree of interpatient variability in serum ferritin and liver iron content (LIC). Reasons for this variability are unclear and may be influenced by genes that regulate iron metabolism. We evaluated the association of the copy number of the glutathione S-transferase M1 (GSTM1) gene and degree of iron overload among patients with SCA. We compared LIC in 38 children with SCA and ≥12 lifetime erythrocyte transfusions stratified by GSTM1 genotype. Baseline LIC was measured using magnetic resonance imaging (MRI), R2*MRI within 3 months prior to, and again after, starting iron unloading therapy. After controlling for weight-corrected transfusion burden (mL/kg) and splenectomy, mean pre-chelation LIC (mg/g dry liver dry weight) was similar in all groups: GSTM1 wild-type (WT) (11.45, SD±6.8), heterozygous (8.2, SD±4.52), and homozygous GSTM1 deletion (GSTM1-null; 7.8, SD±6.9, p = 0.09). However, after >12 months of chelation, GSTM1-null genotype subjects had the least decrease in LIC compared to non-null genotype subjects (mean LIC change for GSTM1-null = 0.1 (SD±3.3); versus −0.3 (SD±3.0) and −1.9 (SD±4.9) mg/g liver dry weight for heterozygous and WT, respectively, p = 0.047). GSTM1 homozygous deletion may prevent effective chelation in children with SCA and iron overload.

Comparison of the Reverse-Remodeling Effect of Pharmacological Soluble Guanylate Cyclase Activation With Pressure Unloading in Pathological Myocardial Left Ventricular Hypertrophy.

Background: Pressure unloading induces the regression of left ventricular myocardial hypertrophy (LVH). Recent findings indicate that pharmacological activation of the soluble guanylate cyclase (sGC) – cyclic guanosine monophosphate (cGMP) pathway may also exert reverse-remodeling properties in the myocardium. Therefore, we aimed to investigate the effects of the sGC activator cinaciguat in a rat model of LVH and compare it to the “gold standard” pressure unloading therapy.Methods: Abdominal aortic banding was performed for 6 or 12 weeks. Sham operated animals served as controls. Pressure unloading was induced by removing the aortic constriction after week 6. The animals were treated from week 7 to 12, with 10 mg/kg/day cinaciguat or with placebo p.o., respectively. Cardiac function and morphology were assessed by left ventricular pressure-volume analysis and echocardiography. Additionally, key markers of myocardial hypertrophy, fibrosis, nitro-oxidative stress, apoptosis and cGMP signaling were analyzed.Results: Pressure unloading effectively reversed LVH, decreased collagen accumulation and provided protection against oxidative stress and apoptosis. Regression of LVH was also associated with a full recovery of cardiac function. In contrast, chronic activation of the sGC enzyme by cinaciguat at sustained pressure overload only slightly influenced pre-established hypertrophy. However, it led to increased PKG activity and had a significant impact on interstitial fibrosis, nitro-oxidative stress and apoptosis. Amelioration of the pathological structural alterations prevented the deterioration of LV systolic function (contractility and ejection fraction) and improved myocardial stiffness.Conclusion: Our results indicate that both cinaciguat treatment and pressure unloading evoked anti-remodeling effects and improved LV function, however in a differing manners.

Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model.

Hypertension can impair structure and function of blood vessels. Experimental data describing the reverse remodeling process after a mechanical pressure unloading therapy in the vasculature is limited. We studied the influence of pressure unloading on both the structural and functional alterations of the aorta in a hypertensive rat model. Using isolated thoracic aortic rings in an in-vitro organ bath system, endothelium-dependent and endothelium-independent vasorelaxation were studied 6-weeks or 12-weeks after abdominal aortic banding (aortic banding-6-week or aortic banding-12-week), and 6-weeks after an aortic debanding procedure performed after the sixth experimental week of aortic banding (aortic banding + debanding-12-week). Age-matched rats were sham-operated (sham-6-week or sham-12-week). The aortic morphometry and histological fibrosis were studied, and the mRNA-expression of metalloproteinase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-2, and soluble guanylate cyclase subunits GUCY1a3 and GUCY1b3 were determined. Aortic banding significantly increased systolic, diastolic, and pulse pressures. Structural changes (increased intima-media thickness and area normalized to body weight, aortic collagen content, higher MMP-2 and TIMP-2, and lower GUCY1a3 and GUCY1b3 mRNA-levels) and functional alterations (impaired endothelium-dependent and endothelium-independent vasorelaxation) have already taken place after 6 weeks of aortic banding. Pressure unloading, after established vascular changes, improved vascular function, resulted in reduced collagen content, and decreased both MMP-2 and TIMP-2 mRNA-expression. Pressure-overload-induced vascular changes regressed due to mechanical unloading. Furthermore, debanding leads to a reductive tendency in fibrosis-associated gene expression and collagen accumulation. Collectively, the addition of drugs that target fibrosis to existing hypertensive treatment may present an attractive therapy against vascular remodeling.

Abstract 12925: The Neuro-Mechanical Unloading for Acute Myocardial Infarction Strikingly Reduces the Infarct Size and Prevents Heart Failure in the Long Term (Best of Basic Science Abstract)

Introduction: Although widespread practice of early coronary intervention has reduced the acute phase mortality in myocardial infarct (MI), the late development of heart failure remains increasing at an alarming rate. Left ventricular (LV) assist device (VAD) unloads the heart, thereby decreases oxygen consumption. Vagal nerve stimulation (VNS) exerts a powerful anti-infarct effects. Hypothesis: We hypothesized that the combination of short term VAD (mechanical unloading) and VNS (neural unloading) for the ischemia/reperfusion (IR) model would prevent the late development of heart failure. Methods: In 24 dogs, we occluded the left anterior descending coronary artery for 180min and then reperfused. We unloaded LV with transvascular VAD (Impella®). We administrated transvascular VNS with a pacing catheter in the superior vena cava (10Hz). The neuro-mechanical unloading started at 90min after the onset of ischemia and ended at 60min after reperfusion. We allocated dogs into 4 groups, IR (n=7), VAD (n=6), VNS (n=4) and VAD+VNS (n=5) and compared the infarct size and cardiac function one month after IR. Results: LVAD+VNS normalized LV end-systolic elastance (IR: 6.1±3.3, VAD: 8.1±1.3, VNS: 10.6±4.5, VAD+VNS: 14.9±2.8 mmHg/ml, p&lt;0.05) and maximally lowered LV end-diastolic pressure (EDP) (16.8±6.4, 6.4±1.5, 5.3±3.1, 3.7±0.4 mmHg, p&lt;0.05). NT-proBNP paralleled the changes in LVEDP (3712±1141, 1728±348, 1507±511, 1059±397 mmHg, p&lt;0.05), supporting nearly normalized cardiac function. VAD+VNS strikingly reduced the infarct size by more than 70% (p&lt;0.05, Figure). Conclusions: The combination of short term VAD and VNS prior to reperfusion markedly reduces the infarct size and prevents the late development of heart failure. The fact that we can deliver both VAD and VNS transvascularly indicates that the neuro-mechanical unloading therapy is clinically applicable and would improve the long term survival in post-MI patients with coronary intervention.

Reply to ‘Unloading therapy by intravenous diuretic in chronic heart failure: a double-edged weapon?’

Cardiologia-UTIC, Ospedale S. Giuseppe, Copertino, Lecce, Italy Received 2 September, 2010 Accepted 15 September, 2010 Correspondence to Antonio F. Amico, MD, Cardiologia-UTIC, Ospedale S. Giuseppe, Via Carmiano 5, 73043 Copertino, Lecce, Italy Tel: +39 0832 931511; e-mail: [email protected]

Unloading therapy by intravenous diuretic in chronic heart failure: a double-edged weapon?

A well established part of therapeutic approaches applying to cases of chronic heart failure (CHF) with extreme fluid retention is represented by intensive intravenous (i.v.) therapy with loop diuretics. This kind of therapy, if appropriately modulated according to the individual clinical picture and biohumoral pattern, is able to decrease the abnormally high ventricular filling pressures, thereby relieving the breathlessness while being able to retrieve a suitable urine output, so as to propitiate regression or disappearance of edema without unfavorable influences on renal clearance of nitrogenous compounds. Nevertheless, the intensive i.v. diuretic therapy should be tailored on the basis of a close assessment of baseline hemodynamic data and hemodynamic response to the medications, in addition to the careful diuretic dose titration and cautious evaluation of risk/benefit ratio. Actually, by using this kind of therapy, there is a risk that a tubular or glomerular injury can be generated and that a frequently preexisting renal dysfunction can be aggravated, especially when excessive doses of loop diuretics are being erroneously administered, so as to cause hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have expressly benefitted from intensive unloading therapy. Recently, the genesis of CHF-related progressive renal deterioration has been highlighted by affirming that a major role may be played rather by neurovegetative disorders, that is, by increase in sympathetic tone and abnormalities in kidney's vasomotility than by cardiac inotropism deficiency. The measures, thought to be able to prevent renal arterial constriction and to impede deterioration of glomerular filtration rate (GFR) due to the ischemic-necrotic tubular injury, as occurring in the set of intensive unloading therapy with i.v. furosemide or other loop diuretic, are represented by application of inotropic and renal vasodilator support by dopamine i.v. infusion at low doses or by other inotropic agents provided with recognized renal vasodilator properties and/or by addition to i.v. furosemide of osmotic agents able to expand the hematic volume, so counteracting or minimizing the reflex renal vasoconstriction induced by furosemide-related reduction in intravascular circulating volume: i.v. infusion of small volumes of hypertonic saline solution, as well as administration of albumin, mannitol and/or plasma expanders. Because renal impairment, as developing in the setting of CHF, has proven to represent a very important indicator of adverse outcome, every effort should be addressed to prevent any significant (>25% of basal value) rise in serum creatinine consequent to diuretic unloading therapy or to other procedures (paracentesis of tense ascites, ultrafiltration) aimed at rapid fluid removal in edematous or ascitic CHF or cardiogenetic anasarca. Ultrafiltration, even though a promising technique highly valued for its acknowledged property to obtain a more rapid fluid and weight loss in CHF patients with marked fluid retention, has been demonstrated so far to produce neurohumoral activation, creatinine abnormalities and symptomatic hypotensions similar to those due to i.v. loop diuretics; thus, the hypothesized advantages of this technique remain to be further clarified and confirmed, with regard to its safety profile and cost-effectiveness.

Right Ventricular Dysfunction During Intensive Pharmacologic Unloading Persists After Mechanical Unloading

BackgroundRight ventricular (RV) dysfunction is associated with adverse outcomes in heart failure (HF). Mechanical unloading should be more effective than pharmacologic therapy to reduce RV afterload and improve RV function. We compared RV size and function after aggressive medical unloading therapy to that achieved in the same patients after 3 months of left ventricular assist device (LVAD) support. Methods and ResultsWe studied 20 patients who underwent isolated LVAD placement (9 pulsatile and 11 axial flow). Echocardiograms were performed after inpatient optimization with diuretic and inotropic therapy and compared with studies done after 3 months of LVAD support. After medical optimization right atrial pressure was 11 ± 5 mm Hg, mean pulmonary artery pressure 36 ± 11 mm Hg, pulmonary capillary wedge pressure 23 ± 9 mm Hg, and cardiac index 2.0 ± 0.6 L·min·m2. Preoperatively, RV dysfunction was moderate (2.6 ± 0.9 on a 0 to 4 scale), RV diameter at the base was 3.1 ± 0.6 cm, and mid-RV was 3.5 ± 0.6 cm. After median LVAD support of 123 days (92 to 170), RV size and global RV dysfunction (2.6 ± 0.9) failed to improve, despite reduced RV afterload. ConclusionsRV dysfunction seen on intensive medical therapy persisted after 3 months of LVAD unloading therapy. Selection of candidates for isolated LV support should anticipate persistence of RV dysfunction observed on inotropic therapy.

Prevalence, predictors and prognostic value of acute impairment in renal function during intensive unloading therapy in a community population hospitalized for decompensated heart failure

Chronic heart failure (CHF) is often associated with impaired renal function. Diuretics and vasodilators may lead to aggravated renal dysfunction (ARD), particularly among patients with decompensated CHF. Although the prevalence of ARD has been evaluated in patients awaiting heart transplantation, little is known about ARD in the community sample of CHF patients. Accordingly, we prospectively assessed the prevalence, predictors and prognostic value of ARD in 79 consecutive patients admitted to our general community hospital for decompensated CHF undergoing intensive unloading therapy (intravenous nitroprusside and furosemide). ARD was defined as a >or= 25% increase in serum creatinine between admission and maximal value of >or= 2 mg/dl. Sixteen patients (20%) developed ARD with a mean increase in serum creatinine of 31% (from 1.74 +/- 0.6 to 2.27 +/- 0.9 mg/dl). ARD persisted at 8-day evaluation in seven of 16 subjects (44%) whereas it was reversible in nine (56%). Lower creatinine clearance at baseline [exp beta = 0.93, 95% confidence interval (CI)=0.87-0.99] and the higher dose of furosemide (exp beta=1.02, 95% CI=1.01-1.03) emerged as independent predictors of ARD. During a follow-up of 11 +/- 8 months, death and hospitalization for worsening CHF occurred more frequently in ARD than non-ARD patients (69% versus 17%, P=0.0001; 69% versus 29%, P=0.003, respectively). Persistent ARD was a powerful independent predictor of long-term adverse outcome (odds ratio=11.1; 95% CI=1.12-36.1; P=0.04). Intensive unloading therapy is associated with the development of ARD in one-fifth of the community population hospitalized for decompensated CHF. The magnitude of this phenomenon is not greater than that observed in younger selected populations with advanced CHF, and depends on baseline renal function and increased diuretic dosage. ARD persisting after 8 days from starting intensive unloading is a powerful predictor of subsequent worsened clinical outcome.