Therapy For Right Ventricular Failure Research Articles

Minimally invasive tricuspid valve surgery.

Tricuspid valve disease carries a very unfavorable prognosis when medically treated. Despite that, surgical intervention is still underperformed for tricuspid valve disease due to the reported high morbidity and mortality from a sternotomy approach. This had led to a shift towards maximizing medical therapy for right ventricular failure and, as a result, a more significant delay in surgical referrals with surgical risks when patients are finally referred. Tricuspid valve patients usually have other co-morbidities resulting from their systemic venous congestion and low flow cardiac output. Minimally invasive tricuspid valve surgery provides less tissue injury and, as a result, less trauma during surgery. This provides a hope for both patients and treating doctors to be more open for providing this procedure with less complications. Isolated minimally invasive tricuspid valve surgery is still not performed as widely as expected. This can be partly due to the adverse outcomes historically labelled to tricuspid valve surgery or by the long journey of learning the surgical team would need to commit to with a minimal access approach. In this article we will review the perioperative pathway, and outcomes of isolated minimally invasive tricuspid valve surgery in the available English literature.

Abstract 835: Development of Molecular Targeted Therapy Against Right Ventricular Failure: Evaluation by Transcriptome and i n vivo Analysis

Backgrounds: Right ventricular (RV) failure is a final common pathway in heart failure. But there is no specific therapy for RV failure. Moreover, it remains unclear how RV failure is developed. To develop a novel therapy for RV failure, we focused on the RV specific character and elucidate the function in RV failure. Methods: Microarray analysis using several parts of adult murine heart was conducted and differentially expressed genes (DEGs) were applied to pathway analysis. Molecular mechanism was examined by using rat cardiomyocytes in vitro. To understand the function of target molecule in vivo, we induced RV failure by pulmonary artery constriction (PAC) in mice and the pathway was specifically blocked in the RV failure model. Results: In microarray analysis for upper RV, RV free wall, LV and ventricular septum, 995 genes were statistically extracted as DEG in upper RV. An alternative complement pathway was significantly activated in upper RV and complement factor, and C3a was a potential upstream factor attributable to unique feature of upper RV. Because C3a plays a central role in alternative complement pathway, we examined the direct role of C3a in cardiomyocytes and RV function. Administration of C3a recombinant protein to primary-cultured cardiomyocytes activated the several MAP kinases including ERK, p38 and JNK, via C3a receptor. Mice developed severe RV failure around 14 days after PAC. Surprisingly, administration of C3a receptor antagonist dramatically improved right ventricular contractile dysfunction in PAC mice. C3 (substrate of C3a) deficient PAC mice also attenuated RV contractile dysfunction, fibrotic change and fetal gene expressions. There results indicated that complement factor C3a regulates the unique phenotypes in RV. Chemical or genetical blockade of C3a ameliorates RV dysfunction in PAC mice. Conclusion: We revealed that alternative complement pathway was activated in RV and C3a had a crucial role in the pathogenesis of RV failure. Accordingly, the blockade of C3a pathway would be a potential therapeutic target for RV disorders.

Reversal of right ventricular failure by chronic α1A-subtype adrenergic agonist therapy.

Right ventricular (RV) failure (RVF) is a serious disease with no effective treatment available. We recently reported a disease prevention study showing that chronic stimulation of α1A-adrenergic receptors (α1A-ARs), started at the time of RV injury, prevented the development of RVF. The present study used a clinically relevant disease reversal design to test if chronic α1A-AR stimulation, started after RVF was established, could reverse RVF. RVF was induced surgically by pulmonary artery constriction in mice. Two weeks after pulmonary artery constriction, in vivo RV fractional shortening as assessed by MRI was reduced by half relative to sham-operated controls (25 ± 2%, n = 27, vs. 52 ± 2%, n = 13, P < 10-11). Subsequent chronic treatment with the α1A-AR agonist A61603 for a further 2 wk resulted in a substantial recovery of RV fractional shortening (to 41 ± 2%, n = 17, P < 10-7 by a paired t-test) along with recovery of voluntary exercise capacity. Mechanistically, chronic A61603 treatment resulted in increased activation of the prosurvival kinase ERK, increased abundance of the antiapoptosis factor Bcl-2, and decreased myocyte necrosis evidenced by a decreased serum level of cardiac troponin. Moreover, A61603 treatment caused increased abundance of the antioxidant glutathione peroxidase-1, decreased level of reactive oxygen species, and decreased oxidative modification (carbonylation) of myofilament proteins. Consistent with these effects, A61603 treatment resulted in increased force development by cardiac myofilaments, which might have contributed to increased RV function. These findings suggest that the α1A-AR is a therapeutic target to reverse established RVF. NEW & NOTEWORTHY Currently, there are no effective therapies for right ventricular (RV) failure (RVF). This project evaluated a novel therapy for RVF. In a mouse model of RVF, chronic stimulation of α1A-adrenergic receptors with the agonist A61603 resulted in recovery of in vivo RV function, improved exercise capacity, reduced oxidative stress-related carbonylation of contractile proteins, and increased myofilament force generation. These results suggest that the α1A-adrenergic receptor is a therapeutic target to treat RVF.

Inotropic therapy for right ventricular failure in newborn piglets: effect on contractility, hemodynamics, and interventricular interaction.

To investigate the effect of right ventricular stunning on interventricular relationships in newborn piglets and to determine the effect of three commonly used inotropic treatment strategies. Randomized, placebo-controlled animal study. Aarhus University Hospital, animal laboratory. Twenty-eight newborn (4-d old) farm-bred piglets. Acute right ventricular failure was induced by 10 cycles of alternating 3 minutes of ischemia and reperfusion of the right coronary artery. After right ventricular failure was induced, treatment with epinephrine + milrinone, dopamine + milrinone, dobutamine, or control (saline) was initiated, and the animals were observed for 180 minutes. Right and left ventricular systolic and diastolic variables were measured using pressure-volume loops recorded by conductance catheters. Arterial and central venous pressures were recorded, and cardiac index was determined by placing a flow probe around the pulmonary artery. Whole-body perfusion was evaluated by measuring pH and lactate in arterial blood samples. Induction of right ventricular stunning resulted in decreased ejection fraction (51% ± 4% vs 40% ± 12%, p = 0.0004); caused an interventricular septum deviation, decreased mean arterial pressure (49 ± 10 mm Hg vs 43 ± 11 mm Hg, p = 0.03), and increased blood lactate (1.85 ± 0.6 mM vs 5.79 ± 3.16 mM, p < 0.00001); and led to a decrease in blood pH (7.37 ± 0.08 vs 7.23 ± 0.13, p < 0.00001). A mortality rate greater than 50% was observed in the control group. All inotropic interventions increased contractility significantly in both the left and right ventricle. The effect of dobutamine on right ventricular failure decreased after 30 minutes and was indistinguishable from the control group after 3 hours. Dobutamine-treated animals had lower perfusion pressures and blood pH compared with epinephrine + milrinone and dopamine + milrinone groups. In newborn piglets, dobutamine had a nonsustained effect on right ventricular failure, resulting in decreased contractility and impaired perfusion compared with both dopamine and epinephrine administered in combination with milrinone.

Management of Right Ventricular Failure in Pulmonary Hypertension (and After LVAD Implantation)

Right ventricular failure (RVF) is increasingly recognized as a complicating feature of a number of disease states, including pulmonary arterial hypertension (PAH) and advanced heart failure. It not only contributes to symptoms and complicates management, but also dramatically impacts prognosis. In PAH, early disease detection and institution of PAH therapy can prevent or delay RVF. Once established, therapy for RVF focuses on optimizing afterload reduction with PAH therapy, controlling volume, and judiciously using inotropic support when needed. In patients undergoing implantation of a LVAD, preoperative assessment and management of RVF is critical. Risk factors for the development of RVF after LVAD have been described, and may identify a population best managed with biventricular support. Postoperative management of RVF focuses on supportive therapy, judicious use of inotropes and volume management. Ongoing research may yield insights into specific therapies to prevent or reverse RVF.

Assessment and treatment of right ventricular failure

Right ventricular (RV) failure is a complex problem with poor outcomes. Diagnosis requires a high degree of clinical suspicion, because many of the signs and symptoms of this condition are nonspecific and can be acute or chronic. Identification of the underlying aetiology, which can include pulmonary hypertension, cardiomyopathy, myocardial infarction, congenital or valvular heart disease, and sepsis, is essential. Echocardiography is the technique of choice for first-line assessment, but cardiac MRI is the current gold standard for anatomical and functional assessment of the right ventricle. Therapy for RV failure should be directed at the underlying cause, although management of symptoms is also important. Therapeutic options range from pharmacological treatment to mechanical RV support and heart transplantation. The complex 3D geometry of the right ventricle and its intricate interactions with the left ventricle have left many questions about RV failure unanswered. However, promising new targeted therapies are under development and mechanical support is becoming increasingly feasible. The next decade will be an exciting time for advances in our understanding and management of RV failure.

Management strategies for patients with pulmonary hypertension in the intensive care unit*

Pulmonary hypertension may be encountered in the intensive care unit in patients with critical illnesses such as acute respiratory distress syndrome, left ventricular dysfunction, and pulmonary embolism, as well as after cardiothoracic surgery. Pulmonary hypertension also may be encountered in patients with preexisting pulmonary vascular, lung, liver, or cardiac diseases. The intensive care unit management of patients can prove extremely challenging, particularly when they become hemodynamically unstable. The objective of this review is to discuss the pathogenesis and physiology of pulmonary hypertension and the utility of various diagnostic tools, and to provide recommendations regarding the use of vasopressors and pulmonary vasodilators in intensive care. We undertook a comprehensive review of the literature regarding the management of pulmonary hypertension in the setting of critical illness. We performed a MEDLINE search of articles published from January 1970 to March 2007. Medical subject headings and keywords searched and cross-referenced with each other were: pulmonary hypertension, vasopressor agents, therapeutics, critical illness, intensive care, right ventricular failure, mitral stenosis, prostacyclin, nitric oxide, sildenafil, dopamine, dobutamine, phenylephrine, isoproterenol, and vasopressin. Both human and animal studies related to pulmonary hypertension were reviewed. Pulmonary hypertension presents a particular challenge in critically ill patients, because typical therapies such as volume resuscitation and mechanical ventilation may worsen hemodynamics in patients with pulmonary hypertension and right ventricular failure. Patients with decompensated pulmonary hypertension, including those with pulmonary hypertension associated with cardiothoracic surgery, require therapy for right ventricular failure. Very few human studies have addressed the use of vasopressors and pulmonary vasodilators in these patients, but the use of dobutamine, milrinone, inhaled nitric oxide, and intravenous prostacyclin have the greatest support in the literature. Treatment of pulmonary hypertension resulting from critical illness or chronic lung diseases should address the primary cause of hemodynamic deterioration, and pulmonary vasodilators usually are not necessary.