Metabolomic Signatures Associated With Pulmonary Arterial Hypertension Outcomes.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a complex disease characterized by progressive right ventricular (RV) failure leading to significant morbidity and mortality. Investigating metabolic features and pathways associated with RV dilation, mortality, and measures of disease severity can provide insight into molecular mechanisms, identify subphenotypes, and suggest potential therapeutic targets. METHODS: We collected data from a prospective cohort of PAH participants and performed untargeted metabolomic profiling on 1045 metabolites from circulating blood. Analyses were intended to identify metabolomic differences across a range of common metrics in PAH (eg, dilated versus nondilated RV). Partial least squares discriminant analysis was first applied to assess the distinguishability of relevant outcomes. Significantly altered metabolites were then identified using linear regression, and Cox regression models (as appropriate for the specific outcome) with adjustments for age, sex, body mass index, and PAH cause. Models exploring RV maladaptation were further adjusted for pulmonary vascular resistance. Pathway enrichment analysis was performed to identify significantly dysregulated processes. RESULTS: A total of 117 participants with PAH were included. Partial least squares discriminant analysis showed cluster differentiation between participants with dilated versus nondilated RVs, survivors versus nonsurvivors, and across a range of NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, REVEAL 2.0 composite scores, and 6-minute-walk distances. Polyamine and histidine pathways were associated with differences in RV dilation, mortality, NT-proBNP, REVEAL score, and 6-minute walk distance. Acylcarnitine pathways were associated with NT-proBNP, REVEAL score, and 6-minute walk distance. Sphingomyelin pathways were associated with RV dilation and NT-proBNP after adjustment for pulmonary vascular resistance. CONCLUSIONS: Distinct plasma metabolomic profiles are associated with RV dilation, mortality, and measures of disease severity in PAH. Polyamine, histidine, and sphingomyelin metabolic pathways represent promising candidates for identifying patients at high risk for poor outcomes and investigation into their roles as markers or mediators of disease progression and RV adaptation.

Shear Wave Dispersion Slope of the Liver Can Predict Adverse Outcomes in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH) often causes right-sided heart failure (HF), inducing organ damage. Shear wave elastography (SWE) is a novel ultrasound technique for characterizing tissue. Some studies have reported that shear wave dispersion slope (SWDS) enables the assessment of early hepatic damage in HF. This study aimed to evaluate the prognostic impact of SWDS in patients with PH.This single-center cohort study enrolled 36 patients with PH who underwent SWE at Okayama University Hospital between March 2018 and April 2021. Patients were divided into 2 groups on the basis of the median value of SWDS: low SWDS group (SWDS < 12.4 m/second/kHz, n = 18) and high SWDS group (SWDS ≥ 12.4 m/second/kHz, n = 18). The primary endpoint was the complex of all-cause death or hospitalization for HF. During the follow-up of 391 ± 288 days, all-cause death or hospitalization for HF occurred in 8 patients. One patient died in the low SWDS group. Three patients died and 4 patients were hospitalized for HF in the high group. Kaplan-Meier analysis revealed that the event-free survival rate was significantly worse in the high SWDS group than in the low SWDS group (log-rank, P = 0.01). In univariate Cox proportional hazards analysis, high SWDS was associated with the events (hazard ratio 10.8; 95% confidence interval 1.89-202, P = 0.005).An elevated SWDS was associated with a high rate of events in patients with PH. SWDS has the potential to predict adverse outcomes in patients with PH.

Initial Triple Combination Therapy Including Intravenous Prostaglandin I2 for the Treatment of Patients with Severe Pulmonary Arterial Hypertension.

Upfront combination therapy including intravenous prostaglandin I2 (PGI2-IV) is recognized as the most appropriate treatment for patients with severe pulmonary arterial hypertension (PAH). This retrospective study aimed to determine reasons why this therapy is not used for some patients with severe PAH and describe the hemodynamic and clinical prognoses of patients receiving initial combination treatment with (PGI2-IV+) or without (PGI2-IV-) PGI2-IV.Data for patients with severe PAH (World Health Organization Functional Class III/IV and mean pulmonary arterial pressure [mPAP] ≥ 40 mmHg) were extracted from the Japan Pulmonary Hypertension Registry. Overall, 73 patients were included (PGI2-IV + n = 17; PGI2-IV- n = 56). The PGI2-IV+ cohort was younger than the PGI2-IV- cohort (33.8 ± 10.6 versus 52.6 ± 18.2 years) and had higher mPAP (58.1 ± 12.9 versus 51.8 ± 9.0 mmHg), greater prevalence of idiopathic PAH (88% versus 32%), and less prevalence of connective tissue disease-associated PAH (0% versus 29%). Hemodynamic measures, including mPAP, showed improvement in both cohorts (post-treatment median [interquartile range] 38.5 [17.0-40.0] for the PGI2-IV + cohort and 33.0 [25.0-43.0] mmHg for the PGI2-IV - cohort). Deaths (8/56) and lung transplantation (1/56) occurred only in the PGI2-IV - cohort.These Japanese registry data indicate that older age, lower mPAP, and non-idiopathic PAH may influence clinicians against using upfront combination therapy including PGI2-IV for patients with severe PAH. Early combination therapy including PGI2-IV was associated with improved hemodynamics from baseline, but interpretation is limited by the small sample size.

Work and oxygen consumption of isolated right ventricular papillary muscle in experimental pulmonary hypertension.

Right-sided myocardial mechanical efficiency (work output/metabolic energy input) in pulmonary hypertension can be severely reduced. We determined the contribution of intrinsic myocardial determinants of efficiency using papillary muscle preparations from monocrotaline-induced pulmonary hypertensive (MCT-PH) rats. The hypothesis tested was that efficiency is reduced by mitochondrial dysfunction in addition to increased activation heat reported previously. Right ventricular muscle preparations were subjected to 5 Hz sinusoidal length changes at 37°C. Work and suprabasal oxygen consumption ( V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) were measured before and after cross-bridge inhibition by blebbistatin. Cytosolic cytochrome c concentration, myocyte cross-sectional area, proton permeability of the inner mitochondrial membrane and monoamine oxidase and glucose 6-phosphate dehydrogenase activities and phosphatidylglycerol/cardiolipin contents were determined. Mechanical efficiency ranged from 23% to 11% in control (n = 6) and from 22% to 1% in MCT-PH (n = 15) and correlated with work (r2  = 0.68, P < 0.0001) but not with V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ (r2  = 0.004, P = 0.7919). V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ for cross-bridge cycling was proportional to work (r2  = 0.56, P = 0.0005). Blebbistatin-resistant V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ (r2  = 0.32, P = 0.0167) and proton permeability of the mitochondrial inner membrane (r2  = 0.36, P = 0.0110) correlated inversely with efficiency. Together, these variables explained the variance of efficiency (coefficient of multiple determination r2  = 0.79, P = 0.0001). Cytosolic cytochrome c correlated inversely with work (r2  = 0.28, P = 0.0391), but not with efficiency (r2  = 0.20, P = 0.0867). Glucose 6-phosphate dehydrogenase, monoamine oxidase and phosphatidylglycerol/cardiolipin increased in the right ventricular wall of MCT-PH but did not correlate with efficiency. Reduced myocardial efficiency in MCT-PH is a result of activation processes and mitochondrial dysfunction. The variance of work and the ratio of activation heat reported previously and blebbistatin-resistant V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ are discussed. KEY POINTS: Mechanical efficiency of right ventricular myocardium is reduced in pulmonary hypertension. Increased energy use for activation processes has been demonstrated previously, but the contribution of mitochondrial dysfunction is unknown. Work and oxygen consumption are determined during work loops. Oxygen consumption for activation and cross-bridge cycling confirm the previous heat measurements. Cytosolic cytochrome c concentration, proton permeability of the mitochondrial inner membrane and phosphatidylglycerol/cardiolipin are increased in experimental pulmonary hypertension. Reduced work and mechanical efficiency are related to mitochondrial dysfunction. Upregulation of the pentose phosphate pathway and a potential gap in the energy balance suggest mitochondrial dysfunction in right ventricular overload is a resiult of the excessive production of reactive oxygen species.

Impact of tolvaptan on improvement of tricuspid regurgitation and right ventricular dimension in patients with right-sided heart failure.

Managing right-sided chronic heart failure (CHF) due to tricuspid regurgitation (TR) remains a clinical challenge. Tolvaptan (TLV), a vasopressin V2 receptor inhibitor, is effective in controlling decompensated HF. However, its effects on right-sided CHF caused by TR are unclear. We sought to clarify the effects of TLV in CHF patients complicated with TR. The cohort consisted of 33 CHF patients with moderate or severe TR and permanent atrial fibrillation, who required hospitalization for HF. We observed 19 patients treated with TLV plus conventional therapies (TLV group) and 14 patients with conventional therapies alone (conventional group). Clinical characteristics, echocardiographic parameters, and laboratory data were investigated. Baseline characteristics were similar between groups. In the TLV group, the severity of TR at admission was 73.7% moderate and 26.3% severe. In the conventional group, these percentages were 85.7% and 14.3%, respectively. During the follow-up, the severity of TR improved in the TLV group (trivial-mild: 52.6%; moderate: 36.8%; severe: 10.5%) (p < 0.01). However, it did not improve in the conventional group (trivial-mild: 21.4%; moderate: 50.0%; severe: 28.6%) (p = 0.08). The diameter of the tricuspid annulus (p < 0.01), basal (p = 0.02), and mid right ventricle (p = 0.04) was reduced at follow-up in the TLV group. Nevertheless, these parameters did not change in the conventional group. Serum creatinine levels were maintained (p = 0.74) in the TLV group, but deteriorated in the conventional group (p = 0.03). TLV reduced right ventricular dimensions and improved TR without deterioration of renal function. Thus, TLV may be a new drug for the treatment of CHF patients with TR.

Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure.

Pulmonary hypertension (PH) is a feature of a variety of diseases and continues to harbor high morbidity and mortality. The main consequence of PH is right-sided heart failure which causes a complex clinical syndrome affecting multiple organ systems including left heart, brain, kidneys, liver, gastrointestinal tract, skeletal muscle, as well as the endocrine, immune, and autonomic systems. Interorgan crosstalk and interdependent mechanisms include hemodynamic consequences such as reduced organ perfusion and congestion as well as maladaptive neurohormonal activation, oxidative stress, hormonal imbalance, and abnormal immune cell signaling. These mechanisms, which may occur in acute, chronic, or acute-on-chronic settings, are common and precipitate adverse functional and structural changes in multiple organs which contribute to increased morbidity and mortality. While the systemic character of PH and right-sided heart failure is often neglected or underestimated, such consequences place additional burden on patients and may represent treatable traits in addition to targeted therapy of PH and underlying causes. Here, we highlight the current state-of-the-art understanding of the systemic consequences of PH and right-sided heart failure on multiple organ systems, focusing on self-perpetuating pathophysiological mechanisms, aspects of increased susceptibility of organ damage, and their reciprocal impact on the course of the disease.

Right-sided heart failure is also associated with transverse tubule remodeling in the left ventricle.

Right-sided heart failure is a common consequence of pulmonary arterial hypertension. Overloading the right ventricle results in right ventricular hypertrophy, which progresses to failure in a process characterized by impaired Ca2+ dynamics and force production that is linked with transverse (t)-tubule remodeling. This also unloads the left ventricle, which consequently atrophies. Experimental left-ventricular unloading can result in t-tubule remodeling, but it is currently unclear if this occurs in right-sided heart failure. In this work, we used a model of monocrotaline (MCT)-induced right heart failure in male rats, using confocal microscopy to investigate cellular remodeling of t-tubules, junctophilin-2 (JPH2), and ryanodine receptor-2 (RyR2). We examined remodeling across tissue anatomical regions of both ventricles: in trabeculae, papillary muscles, and free walls. Our analyses revealed that MCT hearts demonstrated a significant loss of t-tubule periodicity, disruption of the normal sarcomere striated pattern with JPH2 labeling, and also a disorganized striated pattern of RyR2, a feature not previously reported in right heart failure. Remodeling of JPH2 and RyR2 in the MCT heart was more pronounced in papillary muscles and trabeculae compared with free walls, particularly in the left ventricle. We find that these structures, commonly used as ex vivo muscle preparations, are more sensitive to the disease process.NEW & NOTEWORTHY In this work, we demonstrate that t-tubule remodeling occurs in the atrophied left ventricle as well as the overloaded right ventricle after right-side heart failure. Moreover, we identify that t-tubule remodeling in both ventricles is linked to sarcoplasmic reticulum remodeling as indicated by decreased labeling periodicity of both the Ca2+ release channel, RyR2, and the cardiac junction-forming protein, JPH2, that forms a link between the sarcoplasmic reticulum and sarcolemma. Studies developing treatments for right-sided heart failure should consider effects on both the right and left ventricle.

12-Month outcomes of transcatheter tricuspid valve repair with the PASCAL system for severe tricuspid regurgitation.

OBJECTIVES: We investigated the durability of tricuspid regurgitation (TR) reduction and the clinical outcomes through 12 months after transcatheter tricuspid valve repair (TTVr) with the PASCAL Transcatheter Valve Repair System. BACKGROUND: TTVr has rapidly developed and demonstrated favorable acute outcomes, but longer follow-up data are needed. METHODS: Overall, 30 patients (age 77 ± 6 years; 57% female) received PASCAL implantation from September 2017 to May 2019 and completed a clinical follow-up at 12 months. RESULTS: The TR etiology was functional in 25 patients (83%), degenerative in three (10%), and mixed in two (7%). All patients had TR severe or greater (massive or torrential in 80%) and heart failure symptoms (90% in NYHA III or IV) under optimal medical treatment. Single-leaflet device attachment occurred in two patients. Moderate or less TR was achieved in 23/28 patients (82%) at 30 days, which was sustained at 12 months (86%). Two patients underwent repeat TTVr due to residual torrential TR (day 173) and recurrence of severe TR (day 280), respectively. One-year survival rate was 93%; 6 patients required rehospitalization due to acute heart failure. NYHA functional class I or II was achieved in 90% and 6-minute walk distance improved from 275 ± 122 m at baseline to 347 ± 112 m at 12-month (+72 ± 82 m, p < .01). There was no stroke, endocarditis, or device embolization during the follow-up. CONCLUSIONS: Twelve-month outcomes from this multicenter compassionate use experience with the PASCAL System demonstrated high procedural success, acceptable safety, and significant clinical improvement.

Chronic Thromboembolic Pulmonary Hypertension Complicated by Giant Pulmonary Artery Aneurysm.

A pulmonary artery (PA) aneurysm is an extremely rare condition that can be idiopathic or secondary. Only a few reports on giant PA aneurysms associated with chronic thromboembolic pulmonary hypertension (CTEPH) are available in the literature. Here, we present a case of CTEPH associated with a secondary giant PA aneurysm detected by autopsy. A 68-year-old woman was diagnosed with pulmonary hypertension (PH) and a PA aneurysm with a diameter of 7.5 cm 7 years before admission. CTEPH was suspected as the cause of PH; however, she refused to undergo surgical treatment. Although her condition improved temporarily with pulmonary vasodilators, she had recurrence of heart failure and died because of the deterioration of her general condition. An autopsy revealed a giant PA aneurysm without medial degeneration, suggesting a secondary PA aneurysm associated with PH. Histological findings indicated multiple organized thrombi with recanalization in the PA bilaterally, and CTEPH was diagnosed as the cause of PH. Although rare, when a PA aneurysm is detected, it is important to consider that CTEPH might be associated with a giant PA aneurysm. A better understanding of this condition is necessary to improve the therapeutic strategy.

[Intraoperative vascular air embolism : Evidence for risks, diagnostics and treatment]. / Intraoperative vaskuläre Luftembolie : Evidenz bei Risiko, Diagnostik und Therapie.

The entry of gases into the vascular system is called vascular air embolism (VAE). The blocking of the pulmonary circulation by VAE can lead to fulminant right-sided heart failure and cardiocirculatory arrest. A VAE can occur at any time if there is an open connection between the environment and a venous vessel with subatmospheric pressure. This situation occurs during ear nose throat surgery, hip surgery, surgery of the lesser pelvis or breast surgery, if the surgical field is above the level of the heart; however, a VAE can also occur during routine tasks, such as insertion or removal of a central venous catheter or during endoscopic procedures with the insufflation of gas.Because during these procedures VAE is not the main focus of the anesthesia or surgery personnel, in such situations its sudden unexpected occurrence can have severe consequences. In contrast, in cardiac surgery or neurosurgery the risk of intraoperative VAE is much better known. In procedures with a higher risk of a clinically relevant VAE, a patent foramen ovale should be ruled out by preoperative transesophageal echocardiography (TEE). Intraoperatively TEE is the most sensitive procedure not only to detect a VAE but also to visualize the clinical expression, e.g. acute right heart overload.The avoidance of an initial and repeated air embolism is the primary measure to minimize the incidence and severity of VAE.Intraoperatively the following measures should be undertaken: excellent communication between anesthesia and surgery personnel with predetermined actions, maintenance of normal volume, patient positioning with minimal difference in height between heart and head, state of the art surgical technique with closure of potential air entry sites, sufficient detection of air by TEE, repeated jugular vein compression during neurosurgery, intraoperative Trendelenburg positioning of the patient during persisting or clinically evident VAE, differentiated adjustment of ventilatory settings and catecholamine treatment, aspiration of the blood-air mixture (air lock) at the junction of the superior vena cava and right atrium through a large bore central venous line and keeping check of the coagulation status.

Time course of decompensation after angiotensin II and high-salt diet in Balb/CJ mice suggests pulmonary hypertension-induced cardiorenal syndrome.

The genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (ANG II + Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that ANG II + Salt impairs cardiac function and induces cardiac remodeling in male Balb/CJ but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography before treatment and every day for 7 days during treatment with ANG II + Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.

Central Extracorporeal Membrane Oxygenation for Bridging of Right-Sided Heart Failure to Lung Transplantation: A Single-Center Experience and Literature Review.

OBJECTIVE: Right-sided heart failure develops in lung transplantation candidates on prolonged peripheral extracorporeal membrane oxygenation support and is a major determinant of mortality. The use of central venoarterial extracorporeal membrane oxygenation for bridging of right-sided heart failure to lung transplantation was evaluated. DESIGN: Retrospective case series and literature review. SETTING: A single tertiary care university hospital. PARTICIPANTS: The study comprised lung transplantation candidates on extracorporeal membrane oxygenation bridging who developed right-sided heart failure. INTERVENTIONS: Central venoarterial extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Of 6 patients who underwent the study protocol, 3 were bridged successfully to lung transplantation and 1 was bridged to recovery. CONCLUSIONS: The study demonstrates that central extracorporeal membrane oxygenation may be a feasible option for bridging of right-sided heart failure to lung transplantation.

Levosimendan ­ a valuable player in the treatment of a right-sided heart failure

A 66 year-old obese man, suffering from type 2 diabetes, high blood pressure, chronic nephropathy in stage 4, permanent atrial fibrillation accompanied by bradycardia was admitted to a cardiology ward with the signs and symptoms of acute right-sided heart failure. A standard therapy was used including combined diuretics therapy. In spite of the applied methods and pharmaceuticals, no significant reduction of the body weight neither improvement in cardiovascular capacity or renal parameters were observed. Due to the ineffectiveness of the standard combined pharmacotherapy applied in the case of the acute circulatory failure, the resistance to diuretics was recognized and as a result of the above, infusion of levosimendan was decided to be applied. This therapy resulted in rich diuresis, significant loss in body weight and considerable improvement in cardiovascular capacity which allowed to continue further diagnostics and appropriate invasive treatment. The article describes current knowledge on the place of levosimendan and its application in the treatment of an right-sided heart failure.

A rare case of intracardiac fibrosarcoma with myxoid features inducing venous occlusion in a dog - a case report.

BACKGROUND: In both humans and animals, cardiac fibrosarcoma is rare among primary cardiac malignant neoplasia. The overall prevalence of cardiac neoplasia in dogs is low, reported to be between 0.17% and 0.19% of hospital admissions. The aim of this report is to describe the clinical and pathological findings of a dog presenting signs of right sided congestive heart failure due to an intracardiac and venous obstructing mass, diagnosed by histopathology as cardiac fibrosarcoma with myxoid features. CASE PRESENTATION: A 7 years old male mix breed Husky weighing 23 kg was presented to our Veterinary Teaching Hospital the owner reporting weight loss, inappetence and exercise intolerance and on presentation exhibited breathlessness and an enlarged abdomen. A 5 minutes six leads electrocardiogram and cardiac ultrasonography were performed using standard, established techniques. Complete blood count, serum liver enzyme activities and renal parameters were assessed. Shortly after the cardiologic examination, the dog died and necropsy examination of the cardiovascular system revealed an elongated and branched mass attached dorsally to the endocardial insertion of the septal tricuspid valve leaflet. This mass extended retrogradely into the lumen of the cervical veins, obstructing the venous flow. Histological diagnosis of the mass was cardiac fibrosarcoma with myxoid features. Multiple metastases were found inside the lungs only. CONCLUSION: This is the first report describing a right cardiac fibrosarcoma with myxoid features and venous obstruction in a dog. Cardiac fibrosarcoma is a rare finding, however should be considered when an intracardiac mass is diagnosed.

Right Ventricular Stroke Work Index.

Recently, long-term outcomes of pre-capillary pulmonary hypertension (PH) have been improved, whereas morbidity and mortality are still high because of right-sided heart failure (HF). Right-sided HF is closely related to right ventricular (RV) function and hemodynamics such as RV stroke work index (RVSWI). However, the association between RVSWI and long-term outcomes in pre-capillary PH has not been well investigated. The aims of this study were to compare clinical characteristics between low RVSWI and high RVSWI and to investigate the association between low RVSWI and long-term outcomes in patients with pre-capillary PH. We included patients admitted to diagnose and evaluate PH by right heart catheterization between 2007 and 2015. Patients with pre-capillary PH were divided into two groups according to the median value of RVSWI (low RVSWI group: RVSWI < 19.7 g・m/m2/beat; high RVSWI group: RVSWI ≥ 19.7 g・m/m2/beat). Kaplan-Meier survival curves were applied to investigate whether the low RVSWI were associated with HF death or HF readmission in patients with pre-capillary PH. A total of 36 patients with pre-capillary PH who were diagnosed as pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH) were allocated into the low RVSWI group (n = 18) and high RVSWI group (n = 18). The event-free survival rate was significantly lower in the low RVSWI group as compared with the high RVSWI group (P = 0.02). In conclusion, lower RVSWI was significantly associated with HF death or HF readmission in patients with PAH or CTEPH.

Current status of percutaneous right ventricular assist devices: First-in-man use of a novel dual lumen cannula.

Ventricular assist devices have become an accepted therapeutic solution for patients with severe left ventricular dysfunction when pharmacology fails to maintain sufficient cardiac output. Despite various technologies that have allowed left ventricular assist devices to become more reliable and versatile in the past decade, comparatively little attention has been applied to right heart assistance which is still in the early stage of its development. The extracorporeal devices developed thus far have been associated with mobility issues and complications common to ventricular assist devices in general, such as infection, bleeding, and thromboembolism. Designed to obviate the problems previously experienced by other right ventricle (RV)-focused devices, the Protek Duo (CardiacAssist, Pittsburgh, PA) is a novel, fully percutaneous, dual lumen cannula for RV support used in conjunction with the paracorporeal TandemHeart(®) (CardiacAssist, Pittsburgh, PA) pump. We describe our initial experience with the Protek Duo cannula in two different clinical scenarios. In addition, we summarize the current percutaneous mechanical support technology for RV assistance and propose modification of current technology to facilitate its application. © 2016 Wiley Periodicals, Inc.

Clinical features, hemodynamics, and outcomes of pulmonary hypertension in adults with coarctation of aorta.

BACKGROUND: Pulmonary hypertension (pH) and secondary right ventricle dysfunction is present in 20 % of adults with coarctation of aorta (COA) based on echocardiographic studies. There are limited data about invasive hemodynamic characterization of PH in COA. The purpose of this study was to delineate the clinical features, hemodynamics, and outcomes of PH in COA. METHOD: Retrospective cohort study of adults with repaired COA that underwent right heart catheterization (RHC). PH was defined as pulmonary artery (PA) mean pressure > 20 mmHg, and PH was classified as isolated precapillary PH and combined pre/postcapillary PH. RESULTS: Of 99 COA patients that underwent RHC, 57 (58 %) had PH. Of the patients with PH, 14 (25 %) had isolated precapillary PH while 43 (75 %) had postcapillary PH with or without precapillary disease. The correlates of PH were PA compliance (adjusted OR 0.79, 95 % CI 0.71-0.86 per 1 ml/mmHg), left atrial reservoir strain (adjusted OR 0.95, 95 % CI 0921-0.98 per 1 %), and atrial fibrillation (adjusted OR 2.18, 95 % CI 1.20-13.5). Higher PA mean pressure was associated with risk of cardiovascular events (adjusted HR 1.04, 95 % CI 1.02-1.06 per 1 mmHg) and all-cause mortality (adjusted HR 1.05, 95 % CI 1.02-1.08 per 1 mmHg). CONCLUSIONS: PH was present in over half of adults with COA referred for RHC, and one-quarter of the patients with PH presented with isolated precapillary PH suggesting an underlying PA vascular dysfunction as a contributing mechanism. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population. CLINICAL SUMMARY: Of 99 adults with repaired coarctation of aorta (COA) that underwent right heart catheterization, 57 % had pulmonary hypertension (pH). Of the patients with PH, 25 % had isolated precapillary PH while 75 % had combined pre/postcapillary PH. The correlates of PH were pulmonary artery (PA) compliance, left atrial reservoir strain and atrial fibrillation. PH was associated with cardiovascular events and all-cause mortality. These data suggest PA vascular dysfunction in addition to left-sided heart disease as potential etiologies for PH in this population. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population.

An Unusual Etiology of Severe Right Heart Failure Deserving of Wider Recognition.

A previously healthy 31-year-old man presented with worsening shortness of breath and a petechial rash. Echocardiography showed severe right-sided heart failure with midsystolic notching of the antegrade right ventricular outflow Doppler envelope suggesting pulmonary hypertension. An extensive work-up revealed scurvy, with a dramatic resolution of symptoms shortly after vitamin C supplementation.