Invasive Hemodynamic Assessment Research Articles

Echocardiography in shock management.

Echocardiography is pivotal in the diagnosis and management of the shocked patient. Important characteristics in the setting of shock are that it is non-invasive and can be rapidly applied.In the acute situation a basic study often yields immediate results allowing for the initiation of therapy, while a follow-up advanced study brings the advantage of further refining the diagnosis and providing an in-depth hemodynamic assessment. Competency in basic critical care echocardiography is now regarded as a mandatory part of critical care training with clear guidelines available. The majority of pathologies found in shocked patients are readily identified using basic level 2D and M-mode echocardiography. A more comprehensive diagnosis can be achieved with advanced levels of competency, for which practice guidelines are also now available. Hemodynamic evaluation and ongoing monitoring are possible with advanced levels of competency, which includes the use of colour Doppler, spectral Doppler, and tissue Doppler imaging and occasionally the use of more recent technological advances such as 3D or speckled tracking.The four core types of shock—cardiogenic, hypovolemic, obstructive, and vasoplegic—can readily be identified by echocardiography. Even within each of the main headings contained in the shock classification, a variety of pathologies may be the cause and echocardiography will differentiate which of these is responsible. Increasingly, as a result of more complex and elderly patients, the shock may be multifactorial, such as a combination of cardiogenic and septic shock or hypovolemia and ventricular outflow obstruction.The diagnostic benefit of echocardiography in the shocked patient is obvious. The increasing prevalence of critical care physicians experienced in advanced techniques means echocardiography often supplants the need for more invasive hemodynamic assessment and monitoring in shock.

109-04: Triple-site pacing cardiac resynchronization therapy in patients with permanent atrial fibrillation: results from a prospective observational study

Purpose: cardiac resynchronization therapy (CRT) still has a significant non-response rate of 30%. In patients with atrial fibrillation (AF) the rate of non-responders is even higher, and few studies focused on this specific subgroup of patients. Triple-site pacing (Tri-V) is a new method of CRT which may help overcome these limitations. We aim to assess the effectiveness of this new type of CRT in patients with permanent AF. Methods: single-center prospective observational study of patients with permanent AF, NYHA class ≥ II and ejection fraction < 35% who underwent CRT implantion. 2 leads were implanted in the right ventricle, one in the apex and another in the outflow tract septal wall. A left ventricle lead was implanted as usual in a conventional CRT. Within 1 month after implantation, all patients underwent minimally invasive hemodynamic assessment using the Vigileo Flotrac® (Edwards Lifesciences) for the determination of cardiac output in Tri-V or conventional biventricular pacing (Bi-V). The final mode (Tri-V vs Bi-V) was programmed according to the hemodynamic performance. Patients follow-up (FUP) was then undertaken at 6 and 12 months, and included clinical assessment with NYHA class determination, quality of life (Qol) assessment with the Minesota QoL questionaire, 6-minute walk test (6MWT) and echocardiogram with determination of the ejection fraction (EF). Patients were classified as responders if NYHA class was reduced by at least one level and EF increase of ≥ 10%, and as super-responders if NYHA class at FUP was I and EF ≥ 50%. Survival rates and survival free of heart failure hospitalization were calculated. For statistical analysis we used the paired samples T test. Summary of Results: we included 40 patients (93% male, mean age 72 ± 10 years). 32 (80%) were programmed in Tri-V based on the hemodynamic test results. The following results pertain to this subgroup. At baseline, 58% of pts were in NYHA class III and 42% NYHA class II, with a mean ejection fraction of 28% ± 5. After completion of 1 year of follow-up, mean QoL score more than halved (31 ± 21 vs. 15 ± 18; p = 0,017 at 12 months), the 6MWT distance was significantly improved in the responder group (416 ± 104 m to 465 ± 107 m, p = 0,005 at 12 months) and the mean ejection fraction also increased (28 ± 5 vs. 40 ± 10; p < 0,001 at 6 months and 28 ± 5 vs. 41 ± 10; p < 0,001 at 12 months). The responder rate was 62% at 6 months and 76% at 12 months. The super-responder rate was 9% at 6 months and 25% at 12 months. 4 pts died. Survival free of of heart failure hospitalization was 87,5%. Conclusion: Tri-V CRT yielded a high response rate, and a much higher super-response rate, than usually reported for conventional CRT in patients with permanent AF. There was a clear improvement in functional capacity and QoL, as well as positive reverse remodeling. These results may warrant considering Tri-V as a first line therapy in patients with permanent AF who are candidates for CRT, or as an upgrade option in non-responders.

Platypnea-Orthodeoxia Syndrome after Transcatheter Aortic Valve Implantation.

Progressive dyspnea and hypoxaemia in the subacute phase after transcatheter aortic valve implantation (TAVI) are uncommon and warrant immediate assessment of valve and prosthesis leaflet function to exclude thrombosis, as well as investigation for other causes related to the procedure, such as left ventricular dysfunction, pulmonary embolism, and respiratory sepsis. In this case, we report the observation of a patient presenting two weeks after TAVI with arterial hypoxaemia in an upright position, relieved by lying flat, and coupled with an intracardiac shunt detected on echocardiography in the absence of pulmonary hypertension, raising the suspicion of Platypnea-Orthodeoxia Syndrome (POS). Invasive intracardiac haemodynamic assessment showed a significant right-to-left shunt (Qp/Qs = 0.74), which confirmed the diagnosis, with subsequent closure of the intracardiac defect resulting in immediate relief of symptoms and hypoxaemia. To our knowledge, this is the first reported case of an interatrial defect and shunt causing Platypnea-Orthodeoxia Syndrome after transcatheter aortic valve implantation, resolved by percutaneous device closure.

Abstract 13551: Invasive Hemodynamic Assessment of Cardiac Output State After MitraClip Therapy

Introduction: MitraClip therapy has become a therapeutic alternative for high surgical risk patients with symptomatic mitral regurgitation (MR). There are limited data about early and no data about later hemodynamic consequences after MR correction and about the impact of elimination of regurgitant flow on cardiac output state . Methods: We studied invasive hemodynamic parameters before operation (conscious non-sedated patients, T1), immediately after MitraClip implantation (still under general anaesthesia, T2) and on day 1 (late) after procedure (conscious, extubated patients, T3) using right heart cathetrization. Results: Of 25 MitraClip patients (72% male; mean age 70y) with functional MR, in 20 were performed invasive measurements in all time points. MitraClip implantation resulted in an increase in cardiac index (CI) from 1.8±0.5 (T1) to 2.4±0.5(T2) and to 3.2±0.5 L/min/m2 (T3), in a decrease in systemic vascular resistance index (SVRI) from 3759±847 (T1) to 2508±551 (T2) and to 1679±360 dyn.s.cm-5/m2 (T3), in a decreese in pulmonary capillary wedge pressure (PCWP) from 17±5 (T1) to 13±5(T2) and to 10±4mmHg(T3), in a decrease in pulmonary vascular resistance index (PVRI) from 598±362 (T1) to 532±260 (T2) and to 363±184 dyn.s.cm-5/m2 (T3), (all p&lt;0.05). Conclusion: MR reduction after successful MitraClip implantation significantly increases CI immediately (27%) and late (75%) and leads to concomitant decrease in SVRI, PVRI and PCWP immediately (33%, 11% and 25%) and late (55%, 39% and 41%) after procedure. No patients showed worsening of cardiac output state immediately (T2) and late (T3) after MR correction.

Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies.

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.

Current developments and future applications of intracoronary hemodynamics.

Intracoronary hemodynamic assessment of the physiologic significance of coronary lesions improves clinical outcomes in patients with coronary artery disease. Coronary flow velocity reserve, fractional flow reserve, instantaneous wave-free ratio, and index of microcirculatory resistance utilize sensor-mounted guidewires to approximate coronary flow. Coronary flow velocity reserve and fractional flow reserve rely on pharmacologic administration of adenosine to achieve hyperemia and diagnose epicardial lesion severity. As an adenosine-free index, the instantaneous wave-free ratio utilizes a wave-free period in the mid-late diastole during which resistance is constant and low to assess lesion significance. The index of microcirculatory resistance combines hyperemic pressure measurements with thermodilution to quantify microvascular resistance. We review the physiology, clinical trials, and clinical applications of these invasive hemodynamic assessments.

Outcome in Heart Failure with Preserved Ejection Fraction: The Role of Myocardial Structure and Right Ventricular Performance.

BackgroundHeart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. Thus, a profound understanding of the pathophysiologic changes in HFpEF is needed to identify risk factors and potential treatment targets in this specific patient population. Therefore, we aimed to comprehensively assess the impact of left- and right-ventricular function and hemodynamics on long-term mortality and morbidity in order to improve risk prediction in patients with HFpEF.Methods and ResultsWe prospectively included 142 consecutive patients with HFpEF into our observational, non-interventional registry. Echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic assessments including myocardial biopsy were performed at baseline. We detected significant correlations between left ventricular extracellular matrix and left ventricular end-diastolic diameter (r = -0.64;p = 0.03) and stroke volume (r = -0.53;p = 0.04). Hospitalization for heart failure and/or cardiac death was observed over a median follow up of 10 months. The strongest risk factors were reduced right ventricular function (adj. HR 6.62;95%CI 3.12- 14.02;p<0.001), systolic pulmonary arterial pressure (adj. HR per 1-SD 1.55;95%CI 1.15- 2.09;p = 0.004) and the pulmonary artery wedge pressure (adj. HR per 1-SD 1.51;95%CI 1.09–2.08; p = 0.012). The area under the ROC curve for right ventricular function was 0.63, for systolic pulmonary arterial pressure 0.75, and for pulmonary artery wedge pressure 0.68.ConclusionThe current study emphasizes the importance of right ventricular function and pulmonary pressures on outcome in patients with HFpEF providing pathophysiological insights into the hemodynamic changes in HFpEF.

Invasive hemodynamic assessments during transcatheter aortic valve implantation: comparison of patient outcomes in higher vs. lower transvalvular gradients with respect to left ventricular ejection fraction

Low-flow and low-gradient (LFLG) aortic stenosis (AS), which can occur with reduced or preserved left ventricular ejection fraction (LVEF), represents a challenging patient subset. Since outcomes in patients with LFLG AS are worse following surgical aortic valve replacement, we analyzed outcomes in patients after transcatheter aortic valve implantation (TAVI) in our large database. Among 841 treated patients, a total of 676 patients with complete dataset of invasive right- and left-sided hemodynamics were analyzed. Patients were subdivided into normal flow, high-gradient AS (NFHG: dPmean >40 mmHg, LVEF > 50%), paradoxical LFLG AS (PLFLG: dPmean ≤ 40 mmHg, LVEF > 50%, stroke volume index ≤ 35 ml/m(2)), and classical LFLG AS (CLFLG: dPmean ≤ 40 mmHg, LVEF ≤ 30%). Finally, global hemodynamics and patient outcomes and were compared. Patients with CLFLG AS had a higher prevalence of comorbidities and much higher logistic euro SCORE (35.8 ± 21.7) compared to PLFLG AS (20.0 ± 13.1) and NFHG AS (17.0 ± 11.9). Despite high procedural success rates in all groups, patients with CLFLG AS demonstrated a much higher 30-day and 1-year mortality (NFHG/PLFLG/CLFLG 30-day: 5.9/9.6/18.3 %; 1-year: 11.4/22.4/38.2%). Nevertheless, nearly all survivors demonstrated an improvement of functional capacity (NYHA class) and a decrease of NTproBNP levels during the follow-up. The higher mortality in patients with CLFLG AS reflects an advanced disease state, possibly indicating a futile condition before TAVI. Nevertheless, high procedural success rates and a functional improvement in nearly all survivors support the concept of TAVI.

Mechanistic insights into the benefits of multisite pacing in cardiac resynchronization therapy: The importance of electrical substrate and rate of left ventricular activation

Multisite pacing (MSP) of the left ventricle is proposed as an alternative to conventional single-site LV pacing in cardiac resynchronization therapy (CRT). Reports on the benefits of MSP have been conflicting. A paradigm whereby not all patients derive benefit from MSP is emerging. We sought to compare the hemodynamic and electrical effects of MSP with the aim of identifying a subgroup of patients more likely to derive benefit from MSP. Sixteen patients with implanted CRT systems incorporating a quadripolar LV pacing lead were studied. Invasive hemodynamic and electroanatomic assessment was performed during the following rhythms: baseline (non-CRT); biventricular (BIV) pacing delivered via the implanted CRT system (BIV(implanted)); BIV pacing delivered via an alternative temporary LV lead (BIV(alternative)); dual-vein MSP delivered via 2 LV leads; MultiPoint Pacing delivered via 2 vectors of the quadripolar LV lead. Seven patients had an acute hemodynamic response (AHR) of <10% over baseline rhythm with BIV(implanted) and were deemed nonresponders. AHR in responders vs nonresponders was 21.4% ± 10.4% vs 2.0% ± 5.2% (P < .001). In responders, neither form of MSP provided incremental hemodynamic benefit over BIV(implanted). Dual-vein MSP (8.8% ± 5.7%; P = .036 vs BIV(implanted)) and MultiPoint Pacing (10.0% ± 12.2%; P = .064 vs BIV(implanted)) both improved AHR in nonresponders. Seven of 9 responders to BIV(implanted) had LV endocardial activation characterized by a functional line of block during intrinsic rhythm that was abolished with BIV pacing. All these patients met strict criteria for left bundle branch block (LBBB). No nonresponders exhibited this line of block or met strict criteria for LBBB. Patients not meeting strict criteria for LBBB appear most likely to derive benefit from MSP.

Enhanced Pulmonary Vasodilator Reserve and Abnormal Right Ventricular

Background— Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV–pulmonary artery (PA) functional reserve responses and RV–PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF. Methods and Results— In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV d P /d t max /IP and s′) and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure–flow relationship when compared with controls (all P &lt;0.001). RV–PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction. Conclusions— Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01418248.

Prognostic role of cardiac power index in ambulatory patients with advanced heart failure.

Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (<0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P < 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors.

March 2015 at a glance.

March 2015 at a glance.

Constrictive pericarditis: old disease, new approaches.

Constrictive pericarditis is a disorder of cardiac filling caused by an inelastic pericardium. This treatable cause of heart failure should be considered in all patients with unexplained right heart failure symptoms or signs, especially when the left ventricular ejection fraction is preserved. Diagnosing constrictive pericarditis remains challenging, and the most effective tools are designed to identify its unique pathophysiologic mechanisms: dissociation of intrathoracic and intracardiac pressures and enhanced ventricular interaction. The cornerstone of the diagnostic work-up remains comprehensive echocardiography with Doppler, but cross-sectional imaging and invasive hemodynamic assessment may be necessary in some cases. Cardiac MRI is particularly helpful in identifying those patients who may have inflammatory constriction that would resolve with anti-inflammatory therapy. Complete surgical pericardiectomy remains the only definitive treatment for patients with chronic constriction.

Right Ventricle Functional Assessment

This review explores the historical development of conductance catheterization of the human right ventricle (RV) and its current diagnostic role in assessing RV function in an era of contemporary noninvasive imaging. Significant advances in echocardiography, cardiothoracic computed tomography, and cardiac magnetic resonance in the last decade have led a paradigm shift away from invasive hemodynamic assessment toward noninvasive measurement of RV function. However, imaging modalities are not without some disadvantages. For example, they do not provide the beat-to-beat pressure-volume assessment that is obtained by conductance catheterization, which is still arguably the gold standard for measuring cardiac performance. Right heart catheterization remains an integral part of the assessment of patients with RV dysfunction, and a burgeoning interest in early RV insufficiency in a range of cardiopulmonary diseases has brought the detailed interrogation of RV function back into focus. Although conductance volume assessment of the RV is more limited than the left ventricle, the scope for improving the understanding of RV adaptation to pulmonary and valvular pathologies and RV myocardial disease by using a conductance catheter still exists. We review the up-to-date functional applications of echocardiography and computed tomography/cardiac magnetic resonance to assess the RV and illustrate the potential of contemporary conductance catheter techniques to complement noninvasive imaging in the assessment of RV function.

Relation of Novel Echocardiographic Measures to Invasive Hemodynamic Assessment in Scleroderma‐Associated Pulmonary Arterial Hypertension

Systemic sclerosis (SSC; scleroderma)-associated pulmonary arterial hypertension (PAH) is a major cause of mortality in SSc patients and represents an important diagnostic and therapeutic target. Our aims were to evaluate the relationship between echocardiogram-derived right-sided heart hemodynamics and gold standard right-sided heart catheterization (RHC) measurements in a scleroderma population and to investigate whether this relationship is modified by a subset of pulmonary hypertension. We performed RHC and echocardiography on the same day, with pulmonary function testing in 21 consecutive subjects with scleroderma and precapillary pulmonary hypertension (mean ± SD age 57 ± 10 years, 81% women). RHC measures, including pulmonary arterial systolic and mean pressure and pulmonary vascular resistance (PVR), correlated strongly with echocardiogram-derived data. RHC-derived PVR was negatively associated with right ventricular (RV) systolic performance, as measured by tricuspid annular plane systolic excursion (TAPSE; rho = -0.70, P < 0.001), tissue Doppler tricuspid s' velocity (rho = -0.68, P = 0.002), and RV fractional area change (rho = -0.78, P < 0.001). Correlations with TAPSE and s' velocity were strengthened when forced vital capacity %/diffusing capacity of the lung for carbon monoxide % ≥1.6 was used to identify pure PAH phenotypes in SSc. Bland-Altman analyses demonstrated strong agreement between RHC and echocardiogram-derived hemodynamic measures. Our findings suggest that echocardiography may play a clinical role in identifying pulmonary hypertension and RV dysfunction noninvasively, particularly in a subset of SSc patients stratified by pulmonary function testing. This method may establish specific disease phenotypes with differential cardiovascular impact and prove useful as a marker of disease progression/risk stratification in SSC patients that warrants further investigation in larger cohorts.

Invasive hemodynamic characterization of heart failure with preserved ejection fraction.

Recent hemodynamic studies have advanced our understanding of heart failure with preserved ejection fraction (HFpEF). Despite improved pathophysiologic insight, clinical trials have failed to identify an effective treatment for HFpEF. Invasive hemodynamic assessment can diagnose or exclude HFpEF, making it invaluable in understanding the basis of the disease. This article reviews the hemodynamic mechanisms underlying HFpEF and how they manifest clinically, discusses invasive hemodynamic assessment as a diagnostic tool, and explores how invasive hemodynamic profiling may allow understanding of pathophysiological differences and inform the design and entry criteria for future trials.

RV stroke work in children with pulmonary arterial hypertension: estimation based on invasive haemodynamic assessment and correlation with outcomes

BackgroundRV performance is an important determinant of outcomes in children with pulmonary arterial hypertension (PAH). RV stroke work (RVSW), the product of mean pulmonary artery pressure and stroke volume, integrates...

Myocardial and anti‐inflammatory effects of chronic bosentan therapy in monocrotaline‐induced pulmonary hypertension

Introduction and ObjectivesEndothelin‐1 antagonists are increasingly used in the treatment of pulmonary hypertension despite the lack of knowledge of their myocardial and systemic effects. We assessed the right ventricular myocardial and systemic effects of endothelin‐1 antagonists in monocrotaline‐induced pulmonary hypertension. MethodsMale Wistar rats (180–200 g, n=57) randomly received 60 mg/kg monocrotaline or vehicle subcutaneously. Two days later, bosentan was randomly started (300 mg/kg/day) by oral route in a subgroup of monocrotaline‐injected rats, while the other monocrotaline‐injected and control rats received vehicle. At 25–30 days, invasive hemodynamic assessment was performed under anesthesia, arterial blood samples were collected for gas analysis and plasma was extracted for quantification of endothelin‐1, cytokines, nitrates and 6‐keto‐prostaglandin F1α. Right ventricular myocardium was collected for assessment of cyclooxygenase and nitric oxide synthase activity and gene expression. ResultsThe monocrotaline group developed pulmonary hypertension, low cardiac output, right ventricular hypertrophy and dilation, changes in gene expression and inflammatory activation that were attenuated in the group treated with bosentan. From a functional point of view, this group had improved right ventricular function and preserved ventriculo‐vascular coupling, without deterioration in arterial gas parameters or systemic hypotension. In molecular terms, they showed reduced endothelin‐1 and cytokine levels, decreased right ventricular inducible nitric oxide synthase and cyclooxygenase‐2 activity and increased nitrate plasma levels compared with the non‐treated group. ConclusionsIn this study we demonstrate that besides attenuating pulmonary hypertension, bosentan has beneficial hemodynamic, myocardial and anti‐inflammatory effects.

Myocardial and anti-inflammatory effects of chronic bosentan therapy in monocrotaline-induced pulmonary hypertension

Introduction and ObjectivesEndothelin-1 antagonists are increasingly used in the treatment of pulmonary hypertension despite the lack of knowledge of their myocardial and systemic effects. We assessed the right ventricular myocardial and systemic effects of endothelin-1 antagonists in monocrotaline-induced pulmonary hypertension. MethodsMale Wistar rats (180–200 g, n=57) randomly received 60 mg/kg monocrotaline or vehicle subcutaneously. Two days later, bosentan was randomly started (300 mg/kg/day) by oral route in a subgroup of monocrotaline-injected rats, while the other monocrotaline-injected and control rats received vehicle. At 25–30 days, invasive hemodynamic assessment was performed under anesthesia, arterial blood samples were collected for gas analysis and plasma was extracted for quantification of endothelin-1, cytokines, nitrates and 6-keto-prostaglandin F1α. Right ventricular myocardium was collected for assessment of cyclooxygenase and nitric oxide synthase activity and gene expression. ResultsThe monocrotaline group developed pulmonary hypertension, low cardiac output, right ventricular hypertrophy and dilation, changes in gene expression and inflammatory activation that were attenuated in the group treated with bosentan. From a functional point of view, this group had improved right ventricular function and preserved ventriculo-vascular coupling, without deterioration in arterial gas parameters or systemic hypotension. In molecular terms, they showed reduced endothelin-1 and cytokine levels, decreased right ventricular inducible nitric oxide synthase and cyclooxygenase-2 activity and increased nitrate plasma levels compared with the non-treated group. ConclusionsIn this study we demonstrate that besides attenuating pulmonary hypertension, bosentan has beneficial hemodynamic, myocardial and anti-inflammatory effects.

Prognostic value of noninvasive hemodynamic evaluation of the acute effect of levosimendan in advanced heart failure

Optimization of inotropic treatment in worsening heart failure sometimes requires invasive hemodynamic assessment in selected patients. Impedance cardiography (ICG) may be useful for a noninvasive hemodynamic evaluation. ICG was performed in 40 patients (69 ± 8 years; left ventricular ejection fraction 27.5 ± 5.6%; New York Heart Association 3.18 ± 0.34; Interagency Registry for Mechanically Assisted Circulatory Support 5.48 ± 0.96, before and after infusion of Levosimendan (0.1–0.2 µg/kg per min for up to 24 h). Echocardiogram, ICG [measuring cardiac index (CI), total peripheral resistances (TPRs) and thoracic fluid content (TFC)] and plasma levels of brain natriuretic peptide (BNP) were obtained; in nine patients, right heart catheterization was also carried out. When right catheterization and ICG were performed simultaneously, a significant relationship was observed between values of CI and TPR, and between TFC and pulmonary wedge pressure. ICG detected the Levosimendan-induced recovery of the hemodynamic status, associated with improved systolic and diastolic function and reduction in BNP levels. One-year mortality was 4.4%. At multivariate analysis, independent predictors of mortality were: no improvement in the severity of mitral regurgitation, a persistent restrictive filling pattern (E/E’ > 15), a reduction of BNP levels below 30% and a change below 10% in CI, TPR and TFC. When combined, absence of hemodynamic improvement at ICG could predict 1-year mortality with better sensitivity (86%) and specificity (85%) than the combination of echocardiographic and BNP criteria only (sensitivity 80% and specificity 36%). Noninvasive hemodynamic evaluation of heart failure patients during infusion of inodilator drugs is reliable and may help in their prognostic stratification.