Hemodynamic Phenotypes Research Articles

Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension

BackgroundIn this study, we investigated the impact of the new haemodynamic definition of pulmonary arterial hypertension (PAH) as proposed by the 6th PH World Symposium on phenotypes and survival in...

4303Revisiting the weber and ventilatory classifications in heart failure by combining exercise stress echo with gas exchange phenotyping

Abstract Background In heart failure (HF), the Weber and Ventilatory Classes are well acquired landmark reference exercise classifications for quantification of outcome. However, they have not been associated with a thorough hemodynamic phenotyping in the modern HF populations. Methods 194 HF patients with preserved (N=41), mid-range (N=43), and reduced (N=110) ejection fraction and patients with exercise induced-dyspnea and no HF (nonHF, N=77) underwent CPET combined with Echo-Doppler with special attention for the assessment of left atrial dynamics by strain (LAS) analysis, and right ventricular (RV) to pulmonary circulation (PC) coupling assessed by transticuspid annular plane systolic excursion (TAPSE)/pulmonary arterial systolic pressure (PASP) ratio. They were also evaluated in terms of clinical outcome (mortality and HF hospitalization). Results Distribution and variables of interest for Weber Classes were: Class A; n=22 nonHF, no HFpEF, 3 HFmrEF, 3 HFrEF with LAS during exercise of 39±12% and TAPSE/PASP of 0.67±0.21 mm/mmHg; Class B; n=25, 7, 12, 21 with LAS during exercise of 28±14% and TAPSE/PASP of 0.56±0.25 mm/mmHg; Class C: n=27, 25, 20, 48 with LAS during exercise of 24±14% and TAPSE/PASP of 0.46±0.18 mm/mmHg; Class D; n=3, 9, 8, 38 with LAS during exercise of 17±12% and TAPSE/PASP of 0.33±0.14 mm/mmHg and Ventilatory Class I: 59, 24, 22, 39, with LAS during exercise of 31±14% and TAPSE/PASP of 0.55±0.21 mm/mmHg; Class II: 14, 9, 12, 39 with LAS during exercise of 22±13% and TAPSE/PASP of 0.45±0.21 mm/mmHg; Class III: 3, 7, 5, 20 with LAS during exercise of 16±7% and TAPSE/PASP of 0.31±0.09 mm/mmHg; Class IV: 1, 1, 4, 12 with LAS during exercise of 10±6% and TAPSE/PASP of 0.28±0.11 mm/mmHg. Significant differences among each classes in LAS during exercise and peak TAPSE/PASP (P<0.05, respectively) have been observed (Figures A and B). LAS during exercise and peak TAPSE/PASP were positively correlated with peak VO2 (R=0.45 and 0.49, P<0.05, respectively) and also negatively correlated with VE/VCO2 slope (R=−0.49 and −0.55, P<0.05, respectively). Cox proportional hazard regression analyses showed that Weber (HR=3.7, 95% CI 1.7 to 8.0, P<0.001) and Ventilatory Classes (HR=1.7, 95% CI 1.1 to 2.7, P=0.01) were independently associated with the cardiac endpoint after adjustment for age and gender. Clinical stratification according to Weber (A/B or C/D) and Ventilatory (IV or not) Classes clearly differentiated between patients with low and high clinical risk (HR=2.8, 95% CI 1.4 to 5.7, P=0.005, Figure C). Conclusions In patients with HF of any LVEF, Weber and Ventilatory classifications are paralleled by progressive impairment in exercise echo-derived hemodynamic parameters of left atrial function and RV to PC coupling. Peak VO2 and VE/VCO2 slope combine in a strong predictive value irrespective of type of HF.

Hemodynamic Phenotypes of Hypertension Based on Cardiac Output and Systemic Vascular Resistance

Blood pressure is a physiologic measure that reflects cardiac output and systemic vascular resistance. Classification by these components could be useful in characterizing subtypes of hypertension, which may have a role in selecting treatment strategies. However, hemodynamic phenotypes of a large, stable, outpatient population with hypertension remain unknown. We included 34,238 people with systolic blood pressure of ≥130 mm Hg, who underwent impedance cardiography at 51 sites of iKang Health Checkup Centers throughout China between 2012 and 2018. Hemodynamic parameters measured included stroke volume, stroke volume index, heart rate, cardiac output, cardiac index, systemic vascular resistance, and systemic vascular resistance index. We characterized these by systolic blood pressure categories and assessed patient characteristics associated with the ratio of cardiac index to systemic vascular resistance index. Among the study cohort (n = 33,414; mean age 52 ± 13 years; 36.6% female), 49%, 40%, and 11% had systolic blood pressure130-139, 140-159, and ≥160 mm Hg, respectively. Among patients with systolic blood pressure 140-159 mm Hg, 9353 (70%) had high systemic vascular resistance index but normal/low cardiac index, 1949 (15%) had high cardiac index but low/normal systemic vascular resistance index, and 2053 (15%) had low/normal cardiac index and systemic vascular resistance index. Using multivariable analysis, we found that cardiac index to systemic vascular resistance index ratio was negatively associated with age and body mass index (all P <0.05; R-square 0.16, 0.12, and 0.09 for systolic blood pressure 130-139, 140-159 and ≥160 mm Hg, respectively). Different hemodynamic blood pressure phenotypes were identified across all hypertensive blood pressure categories. Although individual characteristics were associated with the cardiac index to systemic vascular resistance index ratio, they only weakly explained the variation.

Vena Caval Flow Regurgitation at Four-dimensional Flow MRI: A New Sign for a Hemodynamic Phenotype of Chronic Obstructive Pulmonary Disease and Emphysema?

Vena Caval Flow Regurgitation at Four-dimensional Flow MRI: A New Sign for a Hemodynamic Phenotype of Chronic Obstructive Pulmonary Disease and Emphysema?

Hypertension Editors' Picks Preeclampsia.

Hypertension Editors' Picks Preeclampsia.

Conventional and Specific-Pathogen Free Rats Respond Differently to Anesthesia and Surgical Trauma

Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Our aim was to examine differences in physiological response in rat colonies bred and housed in a conventional versus SPF facility, and implications for research. Sprague-Dawley rats were anesthetized and catheterized for blood and pressure monitoring, and electrocardiogram (ECG) leads implanted. Hematology was assessed, and coagulation profile using rotational thromboelastometry. Health screening was outsourced to Cerberus Sciences. SPF rats had significantly lower pulse pressure (38% decrease), arrhythmias and prolonged QTc (27% increase) compared to conventional rats. No arrhythmias were found in conventional rats. SPF rats had significantly higher white cell, monocyte, neutrophil and lymphocyte counts, and were hyperfibrinolytic, indicated by EXTEM maximum lysis >15%. Independent assessment revealed similar pathogen exclusion between colonies, with the exception of Proteus in SPF animals. Returning to a conventional facility restored normal host physiology. We conclude that SPF animals displayed an abnormal hemodynamic, hematological and hemostatic phenotype in response to anesthesia and surgery, and provide a number of recommendations to help standardize research outcomes and translation.

Unbiased Phenome-Wide Association Studies of Red Cell Distribution Width Identifies Key Associations with Pulmonary Hypertension.

Rationale: Red cell distribution width (RDW) is a prognostic factor in many diseases; however, its clinical utility remains limited because the relative value of RDW as a biomarker across disease states has not been established. Objectives: To establish an unbiased RDW disease hierarchy to guide the clinical use of RDW and to assess its relationship to cardiovascular hemodynamic and structural parameters. Methods: We performed phenome-wide association studies for RDW in discovery and replication cohorts derived from a deidentified electronic health record in nonanemic individuals. RDW values obtained within 30 days of echocardiogram or right heart catheterization were tested for association with structural and hemodynamic variables. Results: RDW was associated with 263 phenotypes in both men and women in the discovery cohort (n = 121,530), 48 of which replicated in an independent cohort (n = 2,039). The strongest associations were observed with pulmonary arterial hypertension (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.9-2.3), chronic pulmonary heart disease (OR, 2.0; 95% CI, 1.9-2.2), and congestive heart failure (OR, 1.9; 95% CI, 1.8-2.0); P < 1 × 10-74 for all. By echocardiography, RDW was higher in the setting of right ventricular dysfunction than left ventricular dysfunction (P < 0.001). Measured invasively, mean pulmonary arterial pressure was associated with RDW (21 vs. 33 mm Hg at 25th vs. 75th percentile RDW; P < 1 × 10-7) and remained strongly significant even when controlling for mean pulmonary capillary wedge pressure (21 vs. 29 mm Hg at 25th vs. 75th percentile RDW; P < 1 × 10-7). Conclusions: Among 1,364 coded medical conditions, increased RDW was strongly associated with pulmonary hypertension and heart failure. Hemodynamic and echocardiographic phenotyping confirmed these associations and underscored that the most clinically relevant phenotype associated with RDW was pulmonary hypertension. These hypothesis-generating findings highlight the potential shared pathophysiology of pulmonary hypertension and elevated RDW. Elevated RDW in the absence of anemia should alert clinicians to the potential for underlying cardiopulmonary disease.

Proximal pulmonary arterial wall disease in patients with persistent pulmonary hypertension after successful left-sided valve replacement according to the hemodynamic phenotype.

Regression of pulmonary hypertension (PH) is often incomplete after successful left-sided valve replacement (LSVR). Proximal pulmonary arterial (PPA) wall disease can be involved in patients with persistent-PH after LSVR, affecting the right ventricular to pulmonary arterial (RV-PA) coupling. Fifteen patients underwent successful LSVR at least one year ago presenting PH by echo (> 50 mmHg). Prosthesis-patient mismatch and left ventricular dysfunction were discarded. All patients underwent hemodynamic and intravascular ultrasound (IVUS) study. We estimated PPA stiffness (elastic modulus [EM]) and the relative area wall thickness (AWT). Acute vasoreactivity was assessed by inhaled nitric oxide (iNO) testing. RV-PA coupling was estimated by the tricuspid annular plane systolic excursion to systolic pulmonary arterial pressure ratio. Patients were classified as isolated post-capillary PH (Ipc-PH; pulmonary vascular resistance [PVR] ≤ 3 WU and/or diastolic pulmonary gradient [DPG] < 7 mmHg) and combined post- and pre-capillary PH (Cpc-PH; PVR > 3 WU and DPG ≥ 7 mmHg). Both Ipc-PH and Cpc-PH showed a significant increase of EM and AWT. Despite normal PVR and DPG, Ipc-PH had a significant decrease in pulmonary arterial capacitance and RV-PA coupling impairment. Cpc-PH had worse PA stiffness and RV-PA coupling to Ipc-PH (P < 0.05). iNO decreased RV afterload, improving the cardiac index and stroke volume only in Cpc-PH (P < 0.05). Patients with persistent PH after successful LSVR have PPA wall disease and RV-PA coupling impairment beyond the hemodynamic phenotype. Cpc-PH is responsive to iNO, having the worse PA stiffness and RV-PA coupling. The PPA remodeling could be an early event in the natural history of PH associated with left heart disease.

Clinical Implications

Clinical Implications

Hemodynamic phenotypes and its association with blood pressure changes at continuous positive airway pressure therapy in obstructive sleep apnoea hypertensive patients

Background. The goal of our study was to define the hemodynamic phenotypes in hypertensive patients with newly diagnosed obstructive sleep apnoea (OSA) using the individual modelling of hemodynamics derived from ambulatory blood pressure monitoring (ABPM), a method proposed by our group previously, and to assess its validity in blood pressure alterations secondary to continuous positive airway pressure (CPAP). Material and methods. Thirty-three hypertensive patients with moderate-to-severe OSA were investigated. All patients underwent ABPM on two occasions: at baseline and after one week CPAP. The sets of BP indexes at first ABPM were used for individual modelling to define the hemodynamic phenotype (class) based on regression analyses; specifically, the phenotypes were defined for daytime, nighttime and for 24 hours. The CPAP therapy efficacy was predefined as improvement in BP nighttime decrease for additional 5% as compared to baseline ABPM. With reference to this criterion, patients were further classified as responders (who achieved this target), and non-responders. Results. Only 21.2% of hypertensive patients with OSA had optimal hemodynamic phenotype (class H2), despite comprehensive antihypertensive therapy; most of the other patients were classified either as harmonic type (class H3; 39.4%), or of diastolic dysfunctional type (class D3; 15.2%). In the daytime period 18.2% of patients with OSA were classified as D1-class, which is associated with high risk of acute hypotensive episodes. Responders were more frequently characterized by phenotype H3 (daytime) vs. nonresponders: 53.3% and 5.6% respectively; P < 0.05. At nighttime non-responders were more likely to transform the different baseline classes into H3 and D2; P < 0.05 vs. responders. Conclusion. Our study suggest utility of newly developed modelling based on hemodynamic BP indexes in the prediction of BP alterations secondary to CPAP in OSA hypertensive patients.

Abstract P232: Hemodynamic Phenotype and Target Organ Damage in Adolescents With Spurious Hypertension

Objective: Spurious hypertension (sHTN) is characterized by elevated systolic blood pressure (BP) in peripheral arteries measured by office BP and ambulatory BP monitoring (ABPM), but normal central BP. The prevalence of sHTN and its clinical significance remains unknown. The aim of the study was to assess hemodynamics and target organ damage (TOD) in adolescents with sHTN in comparison with other forms of hypertension (HTN). Patients and Methods: We analyzed 265 children (54 girls; 15.1 ±2.5 years) referred with arterial HTN, in whom secondary HTN was excluded. We assessed BP levels - office BP, ABPM, central systolic BP (cSBP), hemodynamics - cardiac output (CO), stroke volume (SV) and target organ damage (TOD) - left ventricular mass index (LVMi), carotid intima-media thickness (cIMT), pulse wave velocity (PWV). Anova with TukeyHSD post hoc test was used for analysis. Results: 115 subjects had white coat hypertension (WCH; office BP&gt;95 th perc+ABPM&lt;95 th perc), 25 had ambulatory prehypertension (preHTN; office BP&lt;95 th perc+ABPM&lt;95 th perc+ABPM load &gt;25%), 43 had sHTN (office BP+ABPM &gt;95th perc+cSBP&lt;95 th perc), 82 had true hypertension (tHTN; office BP+ABPM+cSBP &gt;95th perc. There were no significant differences between groups in age, weight and BMI. Only pts with tHTN presented features typical of hyperkinetic circulation and pts with preHTN presented intermediate hemodynamic phenotype between WCH and sHTN and those with tHTN (p&lt;0.001). Median LVMi ratio to upper limit of normal (g/m 2.7 /95 th percentile by Khoury et. 2009) was similar in both WCH and sHTN (0.82 and 0.80, respectively), and significantly lower than in tHTN (0.89, p=0.04). The proportion of patients with LVH (LVMi&gt;=95 th perc) was 12% in WCH, 4% in preHTN, 9% in sHTN, 22% in tHTN (p=0.05). cIMT Z-scores were also significantly lower in both WCH (0.92) and sHTN (0.90) groups compared to tHTN (1.22, p=0.01). Similar results were obtained for PWV Z-scores (WCH=1.8, sHTN=1.29, tHTN=2.28, p=0.01). Patients with preHT were not significantly different from tHTN patients in all parameters. Conclusions: Adolescents with sHTN have similar hemodynamic phenotype and TOD as patients with WCH. However, because of lack of data on the evolution of sHTN, close monitoring and follow-up is warranted.

Association Between Prepregnancy Cardiovascular Function and Subsequent Preeclampsia or Fetal Growth Restriction.

Preeclampsia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/miscarriage. Few prospective studies have, therefore, been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preeclampsia and fetal growth restriction. Women who subsequently developed preeclampsia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min; P=0.002) and cardiac index (2.9 versus 3.3 L/min per meter2; P=0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg; P=0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm-5; P<0.001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preeclampsia/fetal growth restriction.

Patients with hypertensive responses to exercise or dobutamine stress testing differ in resting hypertensive phenotype

Little is known of the importance of echocardiographic measures of resting systemic vascular resistance (SVR), cardiac output, and diastolic function in the development of a hypertensive response during dobutamine stress echocardiography. We performed a retrospective review of 325 subjects who underwent stress echocardiography and a resting echocardiogram on the same day. Logistical regressions were performed to determine associations between hypertensive response to each type of stress test and clinical and hemodynamic measurements obtained by transthoracic echocardiography. Patients with a hypertensive response to dobutamine or exercise stress modalities had Stage 1 hypertension. Those with a hypertensive response to dobutamine had a significantly elevated SVR and a lower cardiac output compared to those with a hypertensive response to exercise or a nonhypertensive response to dobutamine. An SVR ≥2000 dynes × sec/cm5 showed excellent discrimination between patients who did and did not have a hypertensive response to dobutamine (c = 0.80). A hypertensive response to both stress modalities showed an association with measures of diastolic dysfunction. The hemodynamic and echocardiographic phenotypes of individuals with a hypertensive response to exercise differ from those with a hypertensive response to dobutamine. Further work is necessary to understand and guide antihypertensive therapy when a hypertensive response to stress testing is discovered and to inform choice of stress modality when resting hypertension is present.

Endothelial Cells Exposed to Fluid Shear Stress Support Diffusion Based Maturation of Adult Neural Progenitor Cells.

The neural stem cell (NSC) niche is a highly complex cellular and biochemical milieu supporting proliferating NSCs and neural progenitor cells (NPCs) with close apposition to the vasculature, primarily comprised of endothelial cells (ECs). Current in vitro models of the niche incorporate EC-derived factors, but do not reflect the physiologically relevant hemodynamic state of the ECs or the spatial resolution observed between cells within the niche. In this work, we developed a novel in vitro model of the niche that (1) incorporates ECs cultured with fluid shear stress and (2) fosters paracrine cytokine gradients between ECs and NSCs in a spatiotemporal configuration mimicking the cytoarchitecture of the subventricular niche. A modified cone and plate viscometer was used to generate a shear stress of 10 dynes cm-2 for ECs cultured on a membrane, while statically cultured NPCs are 10 or 1000μm below the ECs. NPCs cultured within 10μm of dynamic ECs exhibit increased PSA-NCAM+ and OLIG2+ cells compared to progenitors in all other culture regimes and the hemodynamic EC phenotype results in distinct progeny phenotypes. This co-culture regime yields greater release of pro-neurogenic factors, suggesting a potential mechanism for the observed progenitor maturation. Based on these results, models incorporating ECs exposed to shear stress allow for paracrine signaling gradients and regulate NPC lineage progression with appropriate niche spatial resolution occurring at 10μm. This model could be used to evaluate cellular or pharmacological interactions within the healthy, diseased, or aged brain.

P2-4 - Clinical Background in Patients With Pulmonary Hypertension Due to Left Heart Disease

Background: Pulmonary hypertension (PH) is a relevant complication of left heart disease (LHD). The 2015 ESC/ERS PH guidelines report two different hemodynamic phenotypes of PH due to LHD (PH-LHD) based on pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG): isolated post-capillary PH (Ipc-PH) and combined post- and pre-capillary PH (Cpc-PH). The objective of this study is to reveal the clinical characterics of Ipc-PH and Cpc-PH. Methods and Results: Among 184 consecutive chronic heart failure patients (averaged age: 64 y.o) who underwent right heart catheterization in our hospital, 62 patients (34%) were identified as PH-LHD. According to the guidelines, Ipc-PH is defined by DPG <7 mmHg and/or PVR ≦ 3 WU and Cpc-PH by DPG ≧ 7 mmHg and/or PVR > 3 WU. Using this definition, we identified three patient groups: Ipc-PH with both normal PVR and DPG (34 pts); Cpc-PH with both increased PVR and DPG (6 pts); and an intermediate group with either increased PVR or DPG (22 pts). Patients with Cpc-PH and the intermediate group had significantly higher mean PA pressure (40 ± 9 vs 31 ± 5 mmHg, P < .001) and lower SvO2 (60 ± 5 vs 69 ± 7%, P < .001) and lower cardiac output compared with the group of patients with Ipc-PH. LVEF in Cpc-PH and the intermediate group tend to be lower than Ipc-PH. Conclusion: Patients with Cpc-PH and the intermediate group have severe clinical background than those with Ipc-PH.

PP.13.02] DETERMINANTS OF CENTRAL HYPERTENSION IN ADOLESCENTS WITH ELEVATED BLOOD PRESSURE – PRELIMINARY RESULTS

Objective: Spurious hypertension (SH) is a phenomenon of elevated blood pressure assessed on the brachial artery with normal values of blood pressure in the aorta. It is assumed that the SH is not connected with target organ damage (TOD) and cardiovascular risk and should not be treated. The aim of the study was to compare the clinical and hemodynamic intermediate phenotypes in adolescents with arterial hypertension (AH) and SH and assess predictors of SH. Design and method: Of 240 students in whom brachial blood pressure were measured, 64 adolescents (27 girls; 14.6 ± 0.7 years), in whom AH was diagnosed based on elevated blood pressured found on 3 independent occasions were included to the study. Left ventricular mass index (LVMi), carotid intima-media thickness (cIMT), pulse wave velocity (PWV), central systolic (cSBP) and pulse pressure (cPP) was measured in all hypertensive children. PWV, cSBP and cPP were assessed using oscillometric device (Vicorder®). Results: AH described as elevated both peripheral and cSBP was confirmed in 32 subjects (50%) [23 boys (62.2%) and 9 girls (33.3%); p = 0.04]. Patients with AH had significantly greater waist circumference (WC), body mass index (BMI), peripheral pulse pressure and cPP, cardiac index and stroke volume of the left ventricle compared with SH children (for all comparisons p < 0.05). Left ventricular hypertrophy (LVH) was found in 15 subjects (9 (28%) with AH and 6 (18.7%) with SH. Elevated BMI, visceral obesity and higher cPP, correlated with cSBP. However, multivariate logistic regression analysis showed that the only predictor of elevated cSBP was the male sex. Conclusions: Of all adolescents diagnosed as AH, SH was found in 50%. Visceral obesity, overweight and symptoms of the hyperkinetic circulation were associated with the diagnosis of AH, but the only predictor of AH was a male sex. However, finding of LVH in 18.7% of subjects with SH needs further studies.

Abstract P482: Different Hemodynamic Phenotypes Of Isolated Systolic Hypertension In Adolescents

Objective: Isolated systolic hypertension (ISH) is a dominant form of primary hypertension (PH) in adolescents. Some of them present with normal central systolic blood pressure (cSBP), a phenomenon called spurious hypertension (sHT). The study was aimed to describe hemodynamics of PH in relation to cSBP, central pulse pressure (cPP) and target organ damage (TOD) in adolescents referred because of PH. Patients and Methods: In 267 children (59 girls; 14.9 ±2.6 years) referred with arterial hypertension, in whom secondary hypertension was excluded, 24 hour ABPM, left ventricular mass index (LVMi), carotid intima-media thickness (cIMT), pulse wave velocity (PWV), cSBP, cPP, cardiac index (CI) and stroke volume (SV) was assessed. 64 age and sex matched normotensive control children were control group. Results: 145 subjects had white coat hypertension (WCH) including 24 with ambulatory prehypertension (ambpreHT). Of 122 hypertensive pts, 39 had ambulatory hypertension (ambHT) and 83 severe ambulatory hypertension (severeHT). Normal cSBP was found in all WCH subject and 23 with ambpreHT. 39 of 122 (32%) hypertensive pts had sHT - 47.4% in those with ambHT and 26.5% with severeHT (p=0.0001). cIMT, LVMi, PWV, cSBP and cPP increased across blood pressure strata from normotension, through sHT to PH with elevated cSBP (all p&lt;0.05). LVMi and cIMT correlated with cSBP (r = 0.220; p = 0.0007; r = 0.14; p = 0.04, respectively) and cPP (r = 0.274; p = 0.0001; r=0.202; p=0.002, respectively). 36 pts with left ventricular hypertrophy (LVH) had greater cPP (52 ±10 mmHg) in comparison with subjects without LVH (47 ±8 mmHg; p = 0.027). Regression analysis revealed cPP as the only predictor of LVMi (r 2 = 0.09, β = 0.143, p = 0.03). ROC area for predictors of LVH revealed similar area under curve for cSBP (0.585), cPP (0.618) and 24h systolic ABPM (0.612). Patients with sHT had greater amplification of pulse pressure than normotensive ones. CI and SV was lowest in normotensive controls, intermediate in sHT patients and highest in patients with elevated cSBP (p&lt;0.05). Conclusions: sHT present with intermediate hemodynamic phenotype between normotension and sustained PH. cSBP and cPP differentiates patients with severeHT and TOD from patients with WCH, ambpreHT and ambHT without TOD

Hemodynamic Phenotyping of Pulmonary Hypertension in Left Heart Failure.

Increased pulmonary venous pressure secondary to left heart disease is the most common cause of pulmonary hypertension (PH). The diagnosis of PH due to left heart disease relies on a clinical probability assessment followed by the invasive measurements of a mean pulmonary artery pressure (PAP) ≥25 mm Hg and mean wedged PAP (PAWP) >15 mm Hg. A combination of mean PAP and mean PAWP defines postcapillary PH. Postcapillary PH is generally associated with a diastolic pulmonary pressure gradient (diastolic PAP minus mean PAWP) <7 mm Hg, a transpulmonary pressure gradient (mean PAP minus mean PAWP) <12 mm Hg, and pulmonary vascular resistance ≤3 Wood units (WU). This combination of criteria defines isolated postcapillary PH. Postcapillary PH with elevated vascular gradients and pulmonary vascular resistance defines combined post- and precapillary PH (Cpc-PH). Postcapillary PH is associated with a decreased survival in proportion to increased pulmonary vascular gradients, decreased pulmonary arterial compliance, and reduced right ventricular function. The Cpc-PH subcategory occurs in 12% to 13% of patients with PH due to left heart disease. Patients with Cpc-PH have severe PH, with higher diastolic pulmonary pressure gradient, transpulmonary pressure gradient, and pulmonary vascular resistance and more pronounced ventilatory responses to exercise, lower pulmonary arterial compliance, depressed right ventricular ejection fraction, and shorter life expectancy than isolated postcapillary PH. Cpc-PH bears similarities to pulmonary arterial hypertension. Whether Cpc-PH is amenable to therapies targeting the pulmonary circulation remains to be tested by properly designed randomized controlled trials.

Hemodynamic characteristics of suspected stroke in the emergency department

BackgroundSystemic hemodynamic characteristics of patients with suspected acute ischemic stroke are poorly described. The objective of this study was to identify baseline hemodynamic characteristics of emergency department (ED) patients with suspected acute stroke. MethodsThis was a planned analysis of the stroke cohort from a multicenter registry of hemodynamic profiling of ED patients. The registry prospectively collected non-invasive hemodynamic measurements of patients with suspicion for acute stroke within 12h of symptom onset. K-means cluster analysis identified hemodynamic phenotypes of all suspected stroke patients, and we performed univariate hemodynamic comparisons based on final diagnoses. ResultsThere were 72 patients with suspected acute stroke, of whom 38 (53%) had a final diagnosis of ischemic stroke, 10 (14%) had hemorrhagic stroke, and 24 (33%) had transient ischemic attack (TIA). Analysis defined three phenotypic clusters based on low or normal cardiac index (CI) and normal or high systemic vascular resistance index (SVRI). Patients with TIA had lower mean CI (2.3L/min/m2) compared to hemorrhagic or ischemic stroke patients (p<0.01). ConclusionsThe study demonstrates the feasibility of defining hemodynamic phenotypes of ED patients with suspected stroke.

Molecular differences in susceptibility of the kidney to sepsis-induced kidney injury

BackgroundSeptic acute kidney injury affects 40–50% of all septic patients. Molecular differences between septic patients with and without acute kidney injury (AKI) are only poorly understood. Here, we investigated gene expression changes that differentiated the subjects who developed septic AKI from those who did not and coupled this approach with traditional parameters of renal physiology.MethodsIn 15 anesthetized, mechanically ventilated and instrumented pigs, progressive sepsis was induced either by peritonitis or by continuous intravenous infusion of Pseudomonas aeruginosa. Animals received standard intensive care including goal-directed hemodynamic management. Analyses were performed on kidneys from sham operated animals, septic pigs without AKI, and pigs with septic AKI. Before, and at 12, 18 and 22 h of progressive sepsis, systemic and renal hemodynamics, cortex microcirculation and plasma IL-6 and TNF-α were measured. At 22 h whole kidney expression of pre-selected genes was analyzed by quantitative Real Time PCR.ResultsAnimals with septic AKI had systemic hemodynamic phenotype (normo- or hyperdynamic) comparable with non-AKI subjects, but demonstrated higher plasma levels of cytokines, an increase in renal vascular resistance and early fall in cortical microcirculatory blood flow. The genes whose expression discriminated septic AKI from non-AKI included Toll like receptor 4 (up-regulated 2.7-fold, P = 0.04); Cyclooxygenase-2 (up-regulated 14.6-fold, P = 0.01), Angiotensin II Receptor (up-regulated 8.1-fold, P = 0.01), Caspase 3 (up-regulated 5.1-fold, P = 0.02), Peroxisome Proliferator-Activated Receptor Gamma, Coactivator 1 Alpha (down-regulated 2-fold, P = 0.02).ConclusionsIn this preliminary experimental study, kidney gene expression was profoundly different in animals that developed septic AKI as opposed to septic animals that did not. The biological functions of the genes differentially expressed support a role of inflammatory overstimulation coupled with metabolic and apoptotic molecular responses in early septic AKI. Cyclooxygenase-2 and angiotensin type 2 receptor-dependent downstream mechanisms appear fruitful targets for future mechanistic research.