Pulmonary Artery Pressure Index Research Articles

SHOCK5: Utilization of an RP Flex Impella to support Right Ventricular Dysfunction post Left Ventricular Assist Device Placement

Background: Right ventricular dysfunction (RVD) during Left Ventricular Assist Device (LVAD) placement is associated with increased morbidity and mortality. Right Ventricular Assist Device (RVAD) implantation has been shown to reduce the severity of RVD and can improve overall outcomes. We describe the first use of the RP Flex Impella (Abiomed, Danvers MA) RVAD to support RVD during durable LVAD HeartMate 3 implantation(Abbott, Chicago, IL). Case: A 68 year old female with a history of postpartum cardiomyopathy on home inotropic support for 4 years presented with acute exacerbation of heart failure in the setting of sustained ventricular tachycardia. She was evaluated for LVAD however preoperatively there were concerns for risk of RVD due to pulmonary artery pressure index (PAPI) 1.5 and echocardiogram with moderate right ventricular (RV) dilation and significantly reduced function which had progressed as compared to prior assessments. It was decided during the pre implant meeting to support the RV given borderline parameters despite high dose inotropic support. The RP flex impella was placed via the right internal jugular vein and provided 2.8L support. A sodium bicarbonate purge was utilized instead of heparin due to bleeding concerns. By postoperative day (POD) 1 epinephrine and inhaled nitric oxide were successfully titrated down to facilitate early extubation and systemic heparin was started with a goal PTT 50-60 along with aspirin 81mg. Central venous pressure (CVP) remained 8-12mmHg with PAPI 1.2-1.9 over the next few days. RV function on echo remained mildly reduced and LVAD parameters and hemodynamics were stable. Based on the ability to wean inotropes with stable hemodynamics, formal wean occurred on POD4 with reduction to 1.5L flow. Hemodynamics remained unchanged with CVP 10, PA 30/15, PAPI 1.5. Low dose milrinone remained for RV support and the Impella was removed POD 5 at bedside without complication. Post removal RV dilation and drop in PIs resulted in iNO therapy, which was quickly transitioned to sildenafil. Inotropes were fully weaned off POD 12 and the patient was discharged to acute rehab on POD 16 off inotropes and on sildenafil. Throughout this course, renal function remained within the patient’s normal range and the patient was ambulatory from POD 6. Conclusion: This experience describes the first use of RP flex impella to support RVD during durable LVAD placement. The RP flex impella offers a small, percutaneous option for RV support with ease of use and easy bedside removal due to small sheath size. Early use of the RP flex, preventing further sequelae of RVD allowed for adequate support, bypassing the need for surgical RVAD and thus a shorter recovery than traditionally required. Additionally this case adds to the growing literature of RVAD utilization to improve outcomes in patients with marginal RV function for a successful durable LVAD.

Beneficial effects of berberine against pulmonary complications of experimental pulmonary arterial hypertension in rats and some relevant mechanisms.

Pulmonary arterial hypertension (PAH) is a severe disease that leads to pulmonary vascular remodeling characterized by a rise in pulmonary vascular resistance and pressure. We assessed the effects of an herbal compound, berberine (BB), and some related mechanisms on PAH in rats. Male Wistar rats were assigned to seven groups: control, monocrotaline (MCT), MCT+vehicle, and MCT+BB (with doses of 10, 20, 30, and 40 mg/kg) groups. Three weeks after induction of PAH by MCT, treatment groups received daily intraperitoneal injections of vehicle or BB for 3 weeks. On Day 43, the right ventricular systolic pressure (RVSP, as an index of pulmonary arterial pressure) and the ratio of RV to LV+septum weight (as RV hypertrophy index, right ventricle hypertrophy [RHVI]) were measured. Inflammatory and oxidative stress indices and histopathology of the lungs were also assessed. RVSP (89.4 ± 8.2 vs. 23 ± 3.3), RVHI (0.63 ± 0.08 vs. 0.26 ± 0.04), and lung inflammatory cytokines TNF-α (2.03 ± 0.25 vs. 1.21 ± 0.3) and IL-6 (8.8 ± 0.59 vs. 6.3 ± 0.95) significantly increased in the MCT group compared to the control group. MCT also raised the level of Malondialdehyde (0.11 ± 0.01 vs. 0.09 ± 0.01) and diminished total antioxidant capacity (6.5 ± 0.51 vs. 8.3 ± 0.62), the activity of superoxide dismutase (1.19 ± 0.22 vs. 1.93 ± 0.2), glutathione peroxidase (0.02 ± 0.002 vs. 0.03 ± 0.005), catalase (2.1 ± 0.29 vs. 2.8 ± 0.20) and Bax/Bcl-2 ratio (0.41 ± 0.07 vs. 0.61 ± 0.09) in the lungs. Treatment with BB significantly recovered all of these alterations. BB ameliorated pulmonary vascular remodeling by decreasing inflammation and fibrosis and increasing apoptosis and antioxidant/oxidant balance. Therefore, this herbal derivative may be considered a therapeutic goal against PAH.

Clinical impact of visually assessed right ventricular dysfunction in patients with septic shock

We retrospectively analyzed data from the Medical Information Mart for Intensive Care-III critical care database to determine whether visually-assessed right ventricular (RV) dysfunction was associated with clinical outcomes in septic shock patients. Associations between visually-assessed RV dysfunction by echocardiography and in-hospital mortality, lethal arrhythmia, and hemodynamic indicators to determine the prognostic value of RV dysfunction in patients with septic shock were analyzed. Propensity score analysis showed RV dysfunction was associated with increased risk of in-hospital death in patients with septic shock (adjusted odds ratio [OR] 2.15; 95% confidence interval [CI] 1.99–2.32; P < 0.001). In multivariate logistic regression analysis, RV dysfunction was associated with in-hospital death (OR 2.19; 95% CI 1.91–2.53; P < 0.001), lethal arrhythmia (OR 2.19; 95% CI 1.34–3.57; P < 0.001), and tendency for increased blood lactate levels (OR 1.31; 95% CI 1.14–1.50; P < 0.001) independent of left ventricular (LV) dysfunction. RV dysfunction was associated with lower cardiac output, pulmonary artery pressure index, and RV stroke work index. In patients with septic shock, visually-assessed RV dysfunction was associated with in-hospital mortality, lethal arrhythmia, and circulatory insufficiency independent of LV dysfunction. Visual assessment of RV dysfunction using echocardiography might help to identify the short-term prognosis of patients with septic shock by reflecting hemodynamic status.

Natural History and Prognosis of Patients with Unrepaired Tricuspid Regurgitation Undergoing Implantation of Left Ventricular Assist Device

We aimed to describe the natural history of left ventricular assist device (LVAD)-supported patients with preimplantation significant tricuspid regurgitation (TR) in a single-center retrospective analysis of LVAD-implanted patients (2008-2019). TR severity was assessed semiqualitatively using color-Doppler flow: insignificant TR (iTR) was defined as none/mild TR and significant TR (sTR) as ≥moderate TR. Included were 121 LVAD-supported patients of which 53% (n = 64) demonstrated sTR preimplantation. Among patients with pre-LVAD implantation sTR and available echocardiographic data, 55% (n = 26) ameliorated their TR severity grade to iTR during the first-year postsurgery and 55% (n = 17) had iTR at 2-year follow-up. On univariate analysis, predictors for TR severity improvement post-LVAD implantation were preimplant lack of atrial fibrillation, reduced inferior vena cavae diameter, and elevated pulmonary vascular resistance. In patients who failed to improve their TR severity grade, we observed a deterioration in right ventricular (RV) function (pulmonary artery pressure index 2.0 [1.7, 2.9], a decline in RV work index 242 [150, 471] mm Hg·L/m2) and higher loop-diuretics dose requirement. At a median of 21 (IQR 8, 40) months follow-up, clinical LVAD-related complications, heart failure-hospitalizations, and overall survival were similar among patients who improved versus failed to improve their TR severity-grade post-LVAD implantation. In conclusion, LVAD implantation is accompanied by a reduction in TR severity in approximately 50% of patients. In patients who failed to improve their TR severity grade, progressive RV dysfunction was observed. Overall, an isolated LVAD implantation in patients with sTR does not adversely affect survival.

Right Ventricular Arterial Elastance is Associated with Prognostic Value in one Year Mortality Following Left Ventricular Assist Device Placement

Background In patients with end-stage heart failure (HF), acute right heart failure (RHF) after left ventricular assist device (LVAD) implantation is known to be a source of significant morbidity and mortality. Previous data identified RV pulsatility load using pulmonary arterial compliance as a marker for 6-month mortality in LVAD patients. We aimed to test whether the right ventricular arterial elastance (RVEa) was associated with increased risk of 1 year mortality after LVAD implantation. Hypothesis Patients with higher RVEa at preimplantation have a higher risk of dying at 1 year. Methods We retrospectively identified 381 patients with complete pre-implant hemodynamics obtained Results The majority of patients (65%) had RVEa≥1 (Fig. 1). When comparing baseline demographics, those with RVEa ≥1 were younger, had a lower proportion of hypertension, coronary artery disease, and more likely to be on inotropes pre-implantation. Those with RVEa ≥1 had lower SV, and pulmonary artery pressure index; and higher mean pulmonary artery pressure, pulmonary wedge capillary pressure and transpulmonary gradient. Multivariate survival analysis adjusted for heart rate, BMI, age, and gender demonstrated the only independent predictor of mortality was RVEa ≥1 (hazard ratio 1.80, [95% CI 1.07 - 3.05], p= 0.028). Conclusions Our multi-institutional study demonstrates that higher RVEa is associated with increased 1 year mortality post-VAD implantation. These data may be generalizable to other academic institutions and warrants further investigation in larger cohorts.

Relationship of Aortic Valve Opening with Preload and Afterload in Patients Supported with Centrifugal Left Ventricular Assist Devices

Aortic valve (AV) opening in patients supported with cfLVADS may be a marker of improved myocardial contractility. We aimed to study if status of aortic valve opening is influenced by right ventricular function, preload and afterload both at rest and exercise with pump speed titration. Patients implanted with an isolated centrifugal cfLVAD undergoing routine right heart catheterisation were recruited. Mean arterial pressure (MAP), mean pulmonary capillary wedge pressure (PCWP) and pulmonary artery pressures were recorded. The pulmonary artery pressure index (PAPI) derived from formula was used as a surrogate for right ventricular function. Aortic valve status was determined by transthoracic echocardiography. Patients then performed graded exercise with supine bicycle ergometer until exhaustion (mean workload 40W) at both baseline and maximum pump speed with all measurements repeated. Patients were divided into two groups: closed or open AV. Thirteen patients were studied, mean age 37.4+/-7.4 yrs. Median NYHA class at time of study was II. Median pump speed at rest was 2600rpm (range 2500-2800). Echo derived baseline left ventricular ejection fraction was similar between both groups, closed AV valve 25+/-7.7, open 24.2+/-8.0%, p=0.86. At rest, there was no significant difference between closed AV and open AV for MAP 82.7+/-6.0 vs 85.2 +/-6.0mmHG, p=0.60, PCWP 14.7+/-0.2 vs 16.8+/-6.0mmHg, p=0.46 and PAPI 2.4+/-0.8 vs 2.9+/-0.9, p=0.33. Similarly, no significant difference was noted in these measures at maximum exercise and at maximum pump speed (median 2925rpm, range 2800-3210). Aortic valve opening in patients supported by cfLVADs is not significantly influenced by afterload or preload at both rest and exercise. The contribution of intrinsic myocardial contractility derived by load independent methods on aortic valve opening is warranted.

Pulmonary vascular response to air-breathing exercise in humans following an 8-h exposure to hypoxia

This study is concerned with the pulmonary vasculature in euoxia after preconditioning with 8h of hypoxia. The particular question we ask is whether the pulmonary vasculature will dilate normally with exercise or retain some degree of vasoconstriction, as has previously been reported in studies involving longer exposures to the hypoxia of high altitude. Ten subjects were studied on two separate days. On one day, subjects were exposed to 8h of isocapnic hypoxia (end-tidal P(O)(2) 55Torr) and on the other day to 8h of euoxia as a control. Before and after each exposure, subjects undertook 20min of exercise at an intensity to elevate heart rate (HR) by approximately 30bpm. During this period, Doppler echocardiography was used to assess the maximum pressure gradient during systole across the tricuspid valve (DeltaP(max)) as an index of pulmonary arterial pressure. Following 8-h hypoxia, but not control, DeltaP(max) increased by approximately 2mmHg with the subjects breathing air at rest (ANOVA, P<0.02). Under control conditions, exercise at approximately 30 bpm above resting HR increased DeltaP(max) by 9.9+/-1.3mmHg (mean+/-SE). Following 8-h hypoxia, but not control, this sensitivity of DeltaP(max) to exercise increased by approximately 35% to 13.4+/-2.1mmHg (P<0.05). We conclude that prior conditioning with 8h of hypoxia impairs the ability of the pulmonary vasculature to dilate normally during exercise.

B-Type Natriuretic Peptide (BNP) and Mitral Velocity E/A Ratio (MV E/A) Are Two Important Noninvasive Functional Indices of Cardiac AL Amyloidosis.

Cardiac AL amyloidosis is characterized as global myocardial dysfunction, oftentimes complicated by pulmonary events during stem cell mobilization and autotransplant. Although BNP or N terminal proBNP has been shown to be prognostically significant for survival following autotransplant, pathophysiologic processes of the heart for elevated levels of these molecules are unclear. In the current study, we sought to evaluate functional cardiac indices assessed by two-dimensional and Doppler echocardiography and to correlate to BNP and clinical events. Evaluations were done on 39 serial echocardiogrmas obtained between July 2006 and July 2007 from 5 patients with established cardiac AL amyloidosis as a part of systemic amyloidosis (3 primary; 2 secondary to free kappa light chain multiple myeloma). Their median age was 78 years (range 48 to 80). One patient presented with pulmonary edema initially and three others developed pulmonary edema (n = 2) or congestion with pleural effusion (n = 1) during the course of therapy. Two patients underwent melphalan-based autotransplant, and three received melphalan 50 mg/m2 up to 2 cycles every 3 months without stem cell infusion. The median BNP at diagnosis was 1110 pg/mL (range, 115 to 2540); right ventricular diastolic diameter (RVDd) 3.8 cm (2.9 to 4.0); left ventricular end diastolic volume (LVEDV) 88 mL (50 to 125); ejection fraction 60% (53 to 77); MV E/A 2 (1.3 to 2.9); right ventricular systolic pressure (RVSP) 48 mmHg (40 to 68). In multiple regression analyses, BNP levels were most significantly correlated to the RVDd, β = 0.58, p < 0.05. The RVSP as a surrogate index of pulmonary arterial pressure was shown most dependent on the left ventricular diastolic filling assessed by the MV E/A (β = 0.93, p < 0.05) that in turn was dependent on the LVEDV (β = 2.68, p < 0.05). None of the myocardial wall measurements and left ventricular indices except these were found to be significant. Although the RVDd was dependent on the RVSP (β = −1.17, p < 0.05), both BNP and RVSP were independent of each other (β = −0.25, p = 0.6). RVSP levels were significantly elevated in 4 patients who had pulmonary complications: 50, 55, 57, 68 mmHg, respectively. The MV E/A was elevated at or above 2.5 at the time of these episodes: 2.5, 2.9, 2.9, 3.7, respectively. Decrease in both BNP and RVSP appeared to be minimally related to improving serum free light chain levels following therapy: β = 0.29, p = 0.08 and β = 0.34, p = 0.05, respectively. There was no correlation between the MV E/A and serum free light chain level either, β = 0.19, p = 0.3. The data suggests that the MV E/A and RVSP may be useful indices for monitoring patients for potential pulmonary complications, and the BNP appears to reflect more of the right-sided heart events. Further studies are needed to confirm the current findings.

Ascites and venous carbon dioxide tensions in juvenile chickens of highly selected genotypes and native strains

A previous study by this group demonstrated that a high carbon dioxide tension in venous blood (pvCO2) of juvenile broiler chickens is a reliable predictor for ascites susceptibility.In a new experiment with five highly selected genetic stocks and two ascites resistant old breeds we studied levels and variability of pvCO2 within each stock at an early age. Effects of different selection traits (principally growth rate) between fast growing sire lines and slower growing dam lines and a commercial hybrid on blood gas (pCO2, pO2) tensions, pH and haematocrit in venous and arterial blood were examined at different ages and compared to values found in ascites resistant breeds. All birds were housed in floor pens in a climate controlled room and subjected to an ascites-predisposing cold environment.From each stock, 16 birds with the highest (high risk: HRc) and 16 birds with the lowest (low risk: LRc) pvCO2 values were selected at 12 days of age. These birds were marked for future blood sampling to determine changes in haematological characteristics with age and to relate these values to ascites susceptibility. At day 14, eight non-selected birds from each stock were randomly chosen for dissection to determine initial pulmonary arterial pressure index (API) values. Subsequently, all birds were allotted to 8 floor pens (13 birds per pen including two HRc and two LRc birds) per stock. Production performances from 104 birds per stock were measured from 16 to 33 days of age (feed intake (FI); feed conversion ratio (FCR); body weight (BW) at day 33). Mortality was recorded during the complete experimental period. At 5 wk of age, all HRc and LRc birds were necropsied and API values were recorded, which was used to classify the severity of the ascites syndrome.A convincing effect of pvCO2 values in juvenile chickens on API at 5 wk of age in modern lines confirmed results obtained in the previous study. At an early age, pvO2 values were much less predictive for high pulmonary pressure induced ascites at wk 5 than pvCO2 values. Hypercapnia combined with low blood pH values and followed by hypoxemia (inducing high haematocrit values) provoked a marked high incidence of ascites and high API values in modern breeds.A total absence of ascitic symptoms within native breeds corresponded with unchanged low API values during ageing from 12 to 33 days of age and with lower pCO2 values in venous and arterial blood compared to modern breeds at all ages. The pvCO2 difference (mean values) between HRc and LRc groups were similar for all modern lines irrespective of age and showed no relationship to growth rate. API, as a reliable indicator for ascites susceptibility, of modern breed chickens correlated with pvCO2 values, but not with growth rate. The high correlation between pvCO2 in juvenile chickens and API values at 5 wk of age indicated that a strong genetic selection pressure on low pvCO2 values at an early age will be an effective method to reduce decisively the occurrence of the ascites syndrome at sea level.

Chronic unilateral occlusion of an extrapulmonary primary bronchus induces pulmonary hypertension syndrome (ascites) in male and female broilers

Previously, it was demonstrated that acute (4 min) and chronic (12 d) occlusion of an extrapulmonary primary bronchus triggers pulmonary hypertension but not pulmonary hypertension syndrome (PHS, ascites) in broilers. The present study was conducted to determine whether a more prolonged period of bronchus occlusion causes PHS similar to that induced by clamping one pulmonary artery. Male and female broiler chicks, 14 to 18 d old, were anesthetized, the thoracic inlet was opened, and a silver clip was positioned to fully obstruct the left extrapulmonary primary bronchus (BRONCHUS CLAMP group) or the left pulmonary artery (PA-CLAMP group). Sham-operated chicks were anesthetized and the thoracic inlet was opened; however, neither the pulmonary artery nor the bronchus was clamped (SHAM group). An electrocardiogram (ECG) was obtained whenever clinical ascites became apparent in individual broilers, or prior to the final necropsy for broilers surviving to the end (Day 36) of the experiment. The right:total ventricular weight ratio (RV:TV) was evaluated as an index of pulmonary arterial pressure. Early post-surgical mortality (up to 21 d of age) was higher in the PA-CLAMP group (27% for males and females combined) than in the BRONCHUS CLAMP (10%) and SHAM (2%) groups. Cumulative ascites mortality (Days 22 to 36) also was higher in the PA-CLAMP group (86% for males, 77% for females) than in the BRONCHUS CLAMP (69% for males, 41% for females) and SHAM (23% for males, 0% for females) groups. Ascitic birds in all treatment groups had higher RV:TV ratios and more negative ECG Lead II S-wave amplitudes than nonascitic birds, reflecting the right ventricular hypertrophy and generalized ventricular dilation typically associated with PHS. These results demonstrate that unilateral bronchus occlusion is an effective experimental model for triggering ascites at a lower incidence than that obtained by occluding one pulmonary artery. Following the onset of pulmonary hypertension, the pathophysiological progression leading to ascites appears to be similar for broilers with either unilateral bronchus or pulmonary artery occlusion.

Arterial oxygenation and pulmonary arterial pressure in healthy neonates and infants at high altitude

We sought to document arterial oxygen saturation relative to changes in the right ventricular pressure/left ventricular pressure ratio (RVP/LVP ratio), an index of pulmonary arterial pressure, in infants born at high altitude. We performed pulse oximetry and echocardiography in 15 healthy infants born in Leadville, Colo. (3100 m), at 6 to 24 hours, 24 to 48 hours, 1 week, 2 months, and 4 months of age. Pulse oximetry was done under conditions of wakefulness, feeding, and active and quiet sleep. All infants received supplemental O2 at delivery and during postnatal transition; all oximetry measurements were performed with infants breathing room air. The mean arterial O2 saturation ranged from 80.6% +/- 5.3% to 91.1% +/- 1.7% during the 4 months. Values fell during the first week after birth and then rose gradually to attain near-birth values at 2 and 4 months of age. Arterial O2 saturation was uniform among behavioral states at 6 to 24 hours and 24 to 48 hours of age. After 1 week of age, values were highest during wakefulness, intermediate during feeding and active sleep, and lowest during quiet sleep. The RVP/LVP ratio remained in the normal or mildly elevated range throughout the study period. We conclude that the RVP/LVP ratio promptly becomes normal at high altitude, and despite low arterial O2 saturation in the first weeks to months after birth, healthy newborn infants at 3100 m show little evidence of acute pulmonary hypertension.