Elevated Pulmonary Capillary Wedge Pressure Research Articles

Incidence, predictors, and clinical course of atrial tachyarrhythmias in patients with pulmonary hypertension.

The prevalence and predictors of atrial tachyarrhythmias (ATa) in patients with pulmonary hypertension (PH) is less well understood. We performed a retrospective study including 311 patients with PH, confirmed by right heart catheterization in our center between 2007 and 2011. Baseline characteristics, clinical, echocardiographic, and hemodynamic data were collected and compared between patients with and without ATa. The mean age was 61 ± 13 years with 64 % females. The mean pulmonary artery pressure (mPAP) was 46 ± 20 mmHg, mean left ventricular ejection fraction (LVEF) was 55 ± 13 %, and mean pulmonary capillary wedge pressure (PCWP) was 19 ± 9 mmHg. Of the 311 patients with PH, 121 (39 %) patients had ATa. Patients with ATa were older (p<0.001) and were more likely to have systemic hypertension (p=0.03), diabetes (p=0.015), coronary artery disease (p<0.001), heart failure (p<0.001), mitral regurgitation (p=0.001), impaired LVEF (p=0.02), and left atrial enlargement (p<0.001). There was no difference in the prevalence of ATa in mild, moderate, or severe PH. The mean PCWP was higher in patients with ATa (17.9 ± 9 vs 20.3 ± 8; p=0.022). In multivariate analysis using Cox-proportional hazard model, the independent predictors of mortality were age (HR 1.05; p=0.003), coronary artery disease (HR 2.34; p=0.047), LVEF (HR 0.793; p=0.023), and mPAP (HR 1.023; p=0.003). ATa are common in patients with PH. Left heart disease, left atrial enlargement, and elevated PCWP but not right atrial enlargement or mPAP predict the occurrence of ATa in patients with PH.

Echocardiography detects elevated left ventricular filling pressures in heart transplant recipients.

Diastolic dysfunction is a recognized complication in heart transplant (HTx) recipients that limits exercise capacity and is a risk factor for mortality. We investigated the ability of echocardiography to detect elevated pulmonary capillary wedge pressure (mean PCWP>15 mmHg) in HTx recipients. This retrospective study comprised HTx recipients with echocardiography and right heart catheterization within 24 hours (n = 100, 113 investigations). Echocardiographic assessment was performed using mitral inflow (E/A ratio, deceleration time [DT], isovolumic relaxation time [IVRT]), tissue Doppler (E/E' lateral) parameters, and the Doppler-estimated pulmonary artery systolic pressure (Doppler PASP). The right atrial pressure (RAP) was estimated based on size and the effect of respiration or sniffing on the inferior vena cava diameter. Cutoff values were determined from a derivation group (n = 57, receiver operator characteristic curve analysis) and evaluated in a test group (n = 56). Elevated PCWP were found in 38%. The RAP and PCWP were both normal in 58 investigations and elevated in 39 investigations (concordance rate of 86.6%). The presence of signs of increased RAP by echocardiography or with three of five parameters (E/A, DT, IVRT, E/E' lateral, and Doppler PASP) reaching the cutoff values ruled in elevated PCWP with positive likelihood ratios ranging from 15.3 to 9. With normal RAP by echocardiography or none of the other parameters reaching cutoff values elevated PCWP can be ruled out with negative likelihood ratios ranging from 0.07 to 0.19. In conclusion, elevated PCWP in HTx recipients can be assessed using echocardiography.

The pulmonary capillary wedge pressure accurately reflects both normal and elevated left atrial pressure

Pulmonary capillary wedge pressure (PCWP) is routinely used as an indirect measure of the left atrial pressure (LAP), although the accuracy of this estimate, especially under pathological hemodynamic conditions, remains controversial. The aim of this prospective study was to investigate the reliability of PCWP for the evaluation of LAP under different hemodynamic conditions. Simultaneous left and right heart catheterization data of 117 patients with pure mitral stenosis, obtained before and immediately after percutaneous mitral comissurotomy, were analyzed. A strong correlation and agreement between PCWP and LAP measurements was demonstrated (correlation coefficient = 0.97, mean bias ± CI, 0.3 ± -3.7 to 4.2 mm Hg). Comparison of measurements performed within a 5-minute interval and those performed simultaneously revealed that simultaneous pressure acquisition yielded better agreement between the 2 methods (bias ± CI, 1.82 ± 1.98 mm Hg). In contrast to previous observations, the discrepancy between the 2 measures did not increase with elevated PCWP. Multiple regression analysis failed to identify hemodynamic confounders of the discrepancy between the 2 pressures. The ability of PCWP to distinguish between normal and elevated LAP (cutoff set at 12 and 15 mm Hg, respectively), as tested by receiver operating characteristics analysis, demonstrated a remarkably high diagnostic accuracy (area under the curve: 0.989 and 0.996, respectively). Although the described limits of agreement may not allow the interchangeability of PCWP and LAP, especially at lower pressure ranges, our data support the clinical use of PCWP as a robust and accurate estimate of LAP.

Effects of an Interatrial Shunt on Rest and Exercise Hemodynamics: Results of a Computer Simulation in Heart Failure

BackgroundA treatment based on an interatrial shunt device has been proposed for counteracting elevated pulmonary capillary wedge pressure (PCWP) in patients with heart failure and mildly reduced or preserved ejection fraction (HFpEF). We tested the theoretical hemodynamic effects of this approach with the use of a previously validated cardiovascular simulation. Methods and ResultsRest and exercise hemodynamics data from 2 previous independent studies of patients with HFpEF were simulated. The theoretical effects of a shunt between the right and left atria (diameter up to 12 mm) were determined. The interatrial shunt lowered PCWP by ∼3 mm Hg under simulated resting conditions (from 10 to 7 mm Hg) and by ∼11 mm Hg under simulated peak exercise conditions (from 28 to 17 mm Hg). Left ventricular cardiac output decreased ∼0.5 L/min at rest and ∼1.3 L/min at peak exercise, with corresponding increases in right ventricular cardiac output. However, because of the reductions in PCWP, right atrial and pulmonary artery pressures did not increase. A majority of these effects were achieved with a shunt diameter of 8–9 mm. The direction of flow though the shunt was left to right in all of the conditions tested. ConclusionsThe interatrial shunt reduced left-sided cardiac output with a marked reduction in PCWP. This approach may reduce the propensity for heart failure exacerbations and allow patients to exercise longer, thus attaining higher heart rates and cardiac outputs with the shunt compared with no shunt. These results support clinical investigation of this approach and point out key factors necessary to evaluate its safety and hemodynamic effectiveness.

Characterization of a Novel Symptom of Advanced Heart Failure: Bendopnea

This study sought to examine the frequency and hemodynamic correlates of shortness of breath when bending forward, a symptom we have termed "bendopnea." Many heart failure patients describe bendopnea such as when putting on their shoes. This symptom has not previously been characterized. We conducted a prospective study of 102 subjects with systolic heart failure referred for right-heart catheterization. Time to onset of bendopnea was measured prior to catheterization. Forty-six subjects also underwent hemodynamic assessment when sitting and bending. Hemodynamic profiles were assigned on the basis of whether pulmonary capillary wedge pressure (PCWP) was ≥ 22 mm Hg and cardiac index (CI) was ≤ 2.2 l/min/m(2). Bendopnea was present in 29 of 102 (28%) subjects with median (25th, 75th percentiles) time to onset of 8 (7, 11) seconds. Subjects with bendopnea had higher supine right atrial pressure (RAP) (p = 0.001) and PCWP (p = 0.0004) than those without bendopnea but similar CI (p = 0.2). RAP and PCWP increased comparably in subjects with and without bendopnea when bending, but CI did not change. In those with, versus without, bendopnea, there was more than a 3-fold higher frequency of a supine hemodynamic profile consisting of elevated PCWP with low CI (55% vs. 16%, respectively, p < 0.001) but no association with a profile of elevated PCWP with normal CI (p = 0.95). Bendopnea is mediated via a further increase in filling pressures during bending when filling pressures are already high, particularly if CI is reduced. Awareness of bendopnea should improve noninvasive assessment of hemodynamics in subjects with heart failure.

Elevated right atrial pressure by echocardiography significantly increases the likelihood of concomitant elevated pulmonary capillary wedge pressure in heart transplant recipients

Background and aim: Diastolic dysfunction is a recognized complication in heart transplant recipients that limits exercise capacity and is a risk factor for mortality. In the present study we investigated the ability of echocardiography to identify patients with increased Pulmonary Capillary Wedge Pressure (PCWP>15 mmHg). Methods: Patients with echocardiography and right heart catheterization within 24 hours were included (n=97, 110 investigations). Echocardiographic estimation of PCWP was performed using mitral [E/A, Deceleration Time (DT), Isovolumic Relaxation Time (IVRT)], pulmonary vein (S/D) and tissue Doppler (E/E') variables. The estimation of Right Atrial Pressure (RAP) was in categories (0, 5, 10, 15, 20 mmHg) and based on the effect of respiration or sniffing on the maximum and minimum Inferior Vena Cava (IVC) diameters. The caval index was calculated [(IVCmax-IVCmin)/IVCmax x 100]. Cut-off values were generated to determine increased PCWP using receiver-operator characteristic curve analysis. Results: The mean±SD age was 36±13 years and 78% were male. Rejection ≥ ISHLT grade 2R was found in 6.3% and elevated PCWP in 39%. The linear relation between catheter PCWP and E/A, S/D, DT, IVRT and lateral wall E/E' was weak with correlation coefficient/p-value 0.52/ 8 mmHg) was observed in 91% of patients with elevated PCWP and 15% of those without. Best diagnostic performance was found using variables related to RAP (Table). The presence of elevated RAP by echocardiography increased the likelihood of elevated PCWP 9.1 fold, and normal RAP reduced the likelihood 5 fold. View this table: Table 1. Diagnostic performance Conclusions: There is a strong concordance between filling pressure in the right and left ventricle in heart transplant recipients. Elevated RAP by echocardiography significantly increases the likelihood of concomitant elevated PCWP.

Exaggerated increase of exercise-induced pulmonary artery pressure in systemic sclerosis patients predominantly results from left ventricular diastolic dysfunction

ObjectiveHigh prevalence of exaggerated pulmonary artery pressure response to exercise (EPAPR) was reported in patients with systemic sclerosis (SSc). However, pathophysiology of this phenomenon has not been well defined. Therefore, we evaluated the frequency and potential aetiology of EPAPR in SSc patients.MethodsWe included 85 patients (79 female, 6 male, mean age 54.3 ± 13.9 years) with SSc. Transthoracic echocardiography followed by exercise Doppler echocardiography (EDE) were performed. A positive EDE was defined when at least 20 mmHg increase of tricuspid regurgitation peak gradient (TRPG) was recorded. Right heart catheterization (RHC) with exercise was performed in positive EDE patients and in subjects with resting TRPG >31 mmHg.ResultsResting TRPG >31 mmHg and/or positive EDE was found in 30 patients and they were referred to RHC. Finally, RHC was performed in 20 patients (16 pts resting TRPG >31 mmHg and 4 others normal resting TRPG and positive EDE). In 12 (60 %) of them an EPAPR with elevated pulmonary capillary wedge pressure (PCWP) was observed. Interestingly, mean left atrium (LA) diameter was greater in an EPAPR with elevated PCWP patients than in subjects with normal exercise response (39.36 ± 5.6 vs. 35.53 ± 3.48, p = 0.03). In EPAPR with elevated PCWP group greater mean value of E/E′ of mitral lateral annulus was observed (7.98 ± 3.35 vs. 6.27 ± 1.94, p = 0.03). In the univariate logistic regression analysis increased LA diameter was significant predictor of EPAPR with elevated PCWP (OR 1.199, 95 % CI 1.029–1.396, p = 0.019).ConclusionsDespite very well-known risk of PAH in systemic sclerosis patients, the excessive increase of PAP during exercise is more commonly caused by left ventricular diastolic dysfunction than pulmonary arterial vasculopathy.

Left ventricular dysfunction with pulmonary hypertension: part 2: prognosis, noninvasive evaluation, treatment, and future research.

Pulmonary hypertension (PH) secondary to left-sided heart disease (Group 2 PH) is a frequent complication of heart failure (HF) that worsens exercise capacity, risk for hospitalization, and survival independent of left-ventricular ejection fraction (LVEF) or stage of HF. Increased pulmonary artery pressure (PAP) in patients with HF often represents a combination of increased left-sided filling pressures (passive component) and elevated pulmonary vascular resistance (PVR) attributable to functional and structural abnormalities of the pulmonary vascular bed (reactive component). The latter may be reversible with standard HF treatment in the earlier stages, when remodeling of the pulmonary vasculature has not set in, and abnormalities in pulmonary arterial tone are the major driver for elevated PVR. However, chronic exposure to elevated pulmonary capillary wedge pressure (PCWP) may lead to permanent changes in the pulmonary arterial bed (irreversible or fixed PH).1 Considering that a number of drug classes have successfully modified the natural history of pulmonary arterial hypertension (Group 1 PH) and demonstrated that intervention is possible even after pulmonary vascular remodeling has occurred,2 Group 2 PH is a natural target for screening and potential intervention in patients with HF. In the second part of this 2-part review, we discuss the prognostic impact of PH in HF, the contemporary diagnostic and evaluation approaches, the current evidence from clinical studies in Group 2 PH, the challenges of appropriate patient selection in clinical trials, and potential ways to overcome these challenges in trial designs. ### Echocardiographic Studies Studies using either right heart catheterization (RHC) or echocardiography for determination of PAP have consistently shown that PH considerably worsens prognosis in HF. Abramson et al3 first reported that tricuspid regurgitation jet velocity >2.5 m/s was associated with 3.4 times higher mortality in 108 patients with dilated cardiomyopathy followed for up to 28 months; hospitalization rate for HF was …

Cardiac Hemodynamics in Men Versus Women During Acute ST-Segment Elevation Myocardial Infarction

Several biologic and clinical factors contribute to the increased 30-day mortality and re-infarction rate in women with ST-segment elevation myocardial infarction (STEMI). Sex differences in cardiac hemodynamic parameters such as pulmonary capillary wedge pressure (PCWP) have not been examined and might play an important role. The objectives of the present study were to examine whether female sex is an independent determinant of PCWP during acute STEMI and whether an elevated PCWP contributes to all-cause 30-day mortality and re-infarction in women. The clinical, angiographic, and hemodynamic features of 470 consecutive patients with STEMI (n= 135 women) undergoing emergency coronary angiography with right-side heart catheterization were evaluated with respect to sex. Women had an elevated PCWP (20 ± 8 vs 16 ± 7 mm Hg, p <0.001) and reduced mixed venous oxygen saturation (67 ± 11% vs 71 ± 9%, p= 0.004). On multivariate analysis, female sex (β= 4.04, 95% confidence interval [CI] 2.04 to 6.04, p <0.001), hypertension (β= 2.07, 95% CI 0.31 to 3.83, p= 0.021), and creatine kinase-estimated infarct size (β= 0.001, 95% CI 0.001 to 0.002, p ≤0.001) were independent predictors of an elevated PCWP. Female sex exerted a minor independent effect on 30-day mortality and re-infarction (odds ratio 2.36, 95% CI 1.25 to 4.46, p= 0.008). However, once PCWP was entered into the mediation model, sex was no longer significant, suggesting that the effect of sex on the post-STEMI outcomes is potentially mediated through PCWP (odds ratio 1.07, 95% CI 1.02 to 1.12, p=0.011). In conclusion, during acute STEMI, women have greater left ventricular filling pressures compared with men, independent of age, hypertension, and infarct size. The biologic explanation for this difference requires additional investigation, although it does not appear to contribute to the increased 30-day mortality and re-infarction rate observed in women.

Noninvasive Predictors of Diastolic Dysfunction in Children after Cardiac Transplant

Purpose Current noninvasive methods of screening for diastolic dysfunction such as two-dimensional echocardiography (ECHO) and brain natriuretic peptide (BNP) levels were used to predict cardiac catheterization (CC) derived hemodynamic data. Methods and Materials Cardiac transplant patients were prospectively enrolled to undergo concurrent ECHOs at the time of CC. Prior IRB approval and informed consent was obtained. CC data included right ventricular end diastolic pressure (RVEDP), and pulmonary capillary wedge pressure (PCWP). A BNP was also drawn. ECHO parameters included left ventricular ejection fraction (EF), mitral inflow E and A waves, deceleration time, isovolumic relaxation time, and lateral and septal Doppler tissue imaging. E/A, lateral mitral E/e' and septal E/e' (E s /e') were calculated. Descriptive analysis was performed with comparisons made using chi-square and ANOVA. Regression analysis was performed to determine associations with PCWP and RVEDP. Results We enrolled 72 subjects, ages 0.8-21 years (median 12.9). The majority, 66/69 (96%), had an EF >50% (3 inadequate images). Acute rejection was present in 9/72 (13%). Evidence of cardiac allograft vasculopathy was found in 10/53 (19%) of subjects who had angiography performed. No single ECHO parameter was associated with both elevated PCWP and RVEDP. However, BNP >100 pg/ml was associated with abnormal PCWP (p=0.016) and RVEDP (p=0.040). E s /e'>10 was associated with abnormal PCWP (p=0.039). Mitral E/A >3 was associated with an abnormal RVEDP (p=0.021). Conclusions This is the largest pediatric study to evaluate diastolic ECHO parameters and BNP in association with elevations in RVEDP and PCWP after transplant. Most ECHO parameters were not associated. Conversely, elevation in BNP was consistently associated with elevation in RVEDP and PCWP. This study suggests mitral E/A and E s /e' may be useful as an adjunct to routine BNP for predicting diastolic dysfunction following cardiac transplant.

Preoperative Cardiac Variables of Diastolic Dysfunction and Clinical Outcomes in Lung Transplant Recipients

Background. Orthotopic lung transplantation is now widely performed in patients with advanced lung disease. Patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation; however, there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function and elevated pretransplant pulmonary pressures. Methods. We reviewed the characteristics of 111 patients who underwent bilateral and unilateral lung transplants from 200 to 2009 in order to evaluate the prognostic significance of preoperative markers of diastolic function, including invasively measured pulmonary capillary wedge pressure (PCWP) and echocardiographic variables of diastolic dysfunction including mitral A > E and A′ > E′. Results. Out of 111 patients, 62 were male (56%) and average age was 54.0 ± 10.5 years. Traditional echocardiographic Doppler variables of abnormal diastolic function, including A′ > E′ and A > E, did not predict adverse events (P = 0.49). Mildly elevated pretransplant PCWP (16–20 mmHg) and moderately/severely elevated PCWP (>20 mmHg) were not associated with adverse clinical events after transplant (P = 0.30). Additionally, all clinical endpoints did not show any statistical significance between the two groups. Conclusions. Pre-lung transplant invasive and echocardiographic findings of elevated pulmonary pressures and abnormal left ventricular diastolic function are not predictive of adverse posttransplant clinical events.

Demographics and Outcomes of Patients Diagnosed With Pulmonary Hypertension With Pulmonary Capillary Wedge Pressures 16 to 18 mm Hg: Insights From the REVEAL Registry

The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) is a multicenter, US-based, observational study of patients diagnosed with group 1 pulmonary hypertension enrolled consecutively from March 2006 to December 2009. Of 3,128 patients in this analysis, inclusion criteria permitted enrollment of 268 patients with mean pulmonary capillary wedge pressure (PCWP) 16 to 18 mm Hg at diagnostic right-sided heart catheterization (RHC) (above currently accepted pulmonary arterial hypertension [PAH] diagnostic criteria). This study compared the demographics and outcomes of those 268 patients with an elevated mean PCWP to patients with a mean PCWP ≤ 15 mm Hg. Demographic characteristics and outcomes were compared for patients with mean PCWP ≤ 12, 13 to 15, and 16 to 18 mm Hg at diagnostic and follow-up RHC. At diagnostic RHC, patients with PCWP 16 to 18 mm Hg were older, had more severe hemodynamic impairments, and were more likely to be obese and have other comorbidities than patients with PCWP ≤ 15 mm Hg. There were no clinically relevant differences in 5-year survival rates from diagnostic RHC regardless of PCWP at diagnosis (≤ 15 mm Hg vs 16-18 mm Hg, P = .07). Two-year survival rates of 108 patients with PAH whose PCWP increased to 19 mm Hg (regardless of PCWP at diagnosis) were significantly lower than that of patients with PAH with PCWP ≤ 18 mm Hg at subsequent RHC. Patients with PCWP 16 to 18 mm Hg who were diagnosed and treated for PAH were older, heavier, and more likely to have comorbidities associated with left ventricular diastolic dysfunction at diagnosis than those with PCWP ≤ 15 mm Hg. Five-year survival rates were similarly low for all PCWP subgroups. ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure

We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. The expression of lysyl oxidase (LOX), which regulates CCL, was assessed by Western blot. Compared with patients with normal pulmonary capillary wedge pressure (≤12 mm Hg; n=16), patients with elevated pulmonary capillary wedge pressure (&gt;12 mm Hg; n=22) exhibited increases of left ventricular chamber stiffness constant, fraction of myocardial volume occupied by total collagen tissue, fraction of myocardial volume occupied by collagen type I fibers, CCL, insoluble stiff collagen, and LOX. Pulmonary capillary wedge pressure was correlated with left ventricular chamber stiffness constant ( r =0.639; P &lt;0.001), insoluble stiff collagen ( r =0.474; P &lt;0.005), CCL ( r =0.625; P &lt;0.001), and LOX ( r =0.410; P &lt;0.05) in all of the patients but not with fraction of myocardial volume occupied by total collagen tissue or fraction of myocardial volume occupied by collagen type I fibers. In addition, CCL was correlated with insoluble stiff collagen ( r =0.612; P &lt;0.005), LOX ( r =0.538; P &lt;0.01), left ventricular chamber stiffness constant ( r =0.535; P &lt;0.005), peak filling rate ( r =−0.343; P &lt;0.05), ejection fraction ( r =−0.430; P &lt;0.01), and amino-terminal propeptide of brain natriuretic peptide ( r =0.421; P &lt;0.05) in all of the patients. These associations were independent of confounding factors. These findings indicate that, in hypertensive patients with stage C heart failure, it is only the quality of collagen (ie, degree of cross-linking) that associates with elevated filling pressures. It is suggested that LOX-mediated excessive CCL facilitates the increase in left ventricular stiffness with the resulting elevation of filling pressures in these patients.

World Health Organization Pulmonary Hypertension Group 2: Pulmonary hypertension due to left heart disease in the adult—a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension encountered in clinical practice today. Although frequently a target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of worse prognosis and disease severity, but whether its primary treatment is beneficial or harmful is unknown. An important step to the future study of this important clinical problem will be to standardize definitions across disciplines to facilitate an evidence base that is interpretable and applicable to clinical practice. In this current statement, we provide an extensive review and interpretation of the current available literature to guide current practice and future investigation. At the request of the Pulmonary Hypertension (PH) Council of the International Society for Heart and Lung Transplantation (ISHLT), a writing group was assembled and tasked to put forth this document as described above. The review process was facilitated through the peer review process of the Journal of Heart and Lung Transplantation and ultimately endorsed by the leadership of the ISHLT PH Council.

Prevalence, Clinical Phenotype, and Outcomes Associated With Normal B-Type Natriuretic Peptide Levels in Heart Failure With Preserved Ejection Fraction

B-type natriuretic peptide (BNP) is used widely to exclude heart failure (HF) in patients with dyspnea. However, most studies of BNP have focused on diagnosing HF with reduced ejection fraction (EF). The aim of this study was to test the hypothesis that a normal BNP level (≤100 pg/ml) is relatively common in HF with preserved EF (HFpEF), a heterogenous disorder commonly associated with obesity. A total of 159 consecutive patients enrolled in the Northwestern University HFpEF Program were prospectively studied. All subjects had symptomatic HF with EF >50% and elevated pulmonary capillary wedge pressure. BNP was tested at baseline in all subjects. Clinical characteristics, echocardiographic parameters, invasive hemodynamics, and outcomes were compared among patients with HFpEF with normal (≤100 pg/ml) versus elevated (>100 pg/ml) BNP. Of the 159 patients with HFpEF, 46 (29%) had BNP ≤100 pg/ml. Subjects with normal BNP were younger, were more often women, had higher rates of obesity and higher body mass index, and less commonly had chronic kidney disease and atrial fibrillation. EFs and pulmonary capillary wedge pressures were similar in the normal and elevated BNP groups (62 ± 7% vs 61 ± 7%, p = 0.67, and 25 ± 8 vs 27 ± 9 mm Hg, p = 0.42, respectively). Elevated BNP was associated with enlarged left atrial volume, worse diastolic function, abnormal right ventricular structure and function, and worse outcomes (e.g., adjusted hazard ratio for HF hospitalization 4.0, 95% confidence interval 1.6 to 9.7, p = 0.003). In conclusion, normal BNP levels were present in 29% of symptomatic outpatients with HFpEF who had elevated pulmonary capillary wedge pressures, and although BNP is useful as a prognostic marker in HFpEF, normal BNP does not exclude the outpatient diagnosis of HFpEF.

Transthoracic Echocardiographic Parameters in the Estimation of Pulmonary Capillary Wedge Pressure in Patients With Present or Previous Heart Failure

Multiple echocardiographic criteria are routinely used for the estimation of left heart filling pressures. We assessed the predictive value of various echocardiographic parameters to estimate the left heart filling pressure and proposed a simplified approach for its evaluation. We collected the clinical, echocardiographic, and invasive hemodynamic data from 93 patients with heart failure who underwent right-sided heart catheterization and transthoracic echocardiography within a 24-hour period. Of these 93 patients, 57% had a left ventricular ejection fraction <50% and 69% had an elevated mean pulmonary capillary wedge pressure of ≥ 15 mm Hg. A mitral E/E' of ≥ 15 had a sensitivity of 55% but a specificity of 96%. A left atrial area of ≥ 20 cm(2) had a sensitivity of 66% and specificity of 89%. A deceleration time <140 ms had a sensitivity of 51% and specificity of 93% to predict a pulmonary capillary wedge pressure of ≥ 15 mm Hg. The combination of E/E' ≥ 15 ± left atrial area of ≥ 20 cm(2) ± deceleration time <140 ms provided a sensitivity of 92% and specificity of 85%. On multivariate analysis, the combination of E/E' ≥ 15, left atrial area of ≥ 20 cm(2), and deceleration time <140 ms was the most significant predictor of a pulmonary capillary wedge pressure of ≥ 15 mm Hg (odds ratio 48, 95% confidence interval 10 to 289, p <0.001). In conclusion, this simplified approach using 3 echocardiographic parameters provides an accurate and a practical approach for the routine estimation of the elevated left heart filling pressure.

Relationship of right- and left-sided filling pressures in patients with advanced heart failure: A 14-year multi-institutional analysis

Jugular venous pressure (JVP) is assessed to estimate volume status in patients with heart failure because right atrial pressure (RAP) reflects pulmonary capillary wedge pressure (PCWP). In a large cohort of heart failure patients spanning 14 years, we sought to further characterize the relationship between RAP and PCWP, including identifying temporal trends, to optimize estimates of PCWP by JVP. We also sought to determine whether the RAP to PCWP relationship impacts post-transplant mortality. Hemodynamic data were obtained from 4,079 patients before cardiac transplantation. Elevated RAP was defined as ≥10 mm Hg and elevated PCWP ≥22 mm Hg. Hemodynamics were "concordant" when both RAP and PCWP were elevated or when both were not elevated. The frequency of concordant hemodynamics was assessed over 3 eras (1993 to 1997, 1998 to 2002, 2003 to 2007). Baseline characteristics were compared among quartiles of the ratio (RAP+1)/PCWP. The association of (RAP+1)/PCWP with 2-year mortality after cardiac transplantation was assessed using multivariate models. The frequency of concordant hemodynamics over time was stable (74%, 72%, 73%; p = 0.4). Increasing (RAP+1)/PCWP was associated with the following variables: female gender; cardiomyopathy etiology besides ischemic or non-ischemic; prior sternotomies; and lower creatinine clearance (p < 0.01 for all). Elevated (RAP+1)/PCWP was associated with post-transplant mortality (relative risk 1.2, 95% confidence interval 1.02 to 1.37, p = 0.02). [corrected] RAP and PCWP remain concordant in most heart failure patients, supporting the ongoing use of JVP to estimate PCWP. Easily identifiable patient characteristics were associated with an increased RAP/PCWP ratio, and their presence should alert clinicians that PCWP may be overestimated by JVP assessment. A higher RAP/PCWP ratio was an adverse risk factor for post-cardiac transplant survival.

Simultaneous Doppler Tracing of Transmitral Inflow and Mitral Annular Velocity as an Estimate of Elevated Left Ventricular Filling Pressure in Patients With Atrial Fibrillation

The time interval between the onset of early transmitral flow velocity (E) and that of early diastolic mitral annular velocity (e') (T(E-e')) is a good predictor of elevated left ventricular (LV) filling pressure in patients with sinus rhythm. Although the evaluation of LV filling pressure using E/e' has been challenging in atrial fibrillation (AF), the usefulness of T(E-e') is unknown. E and e' were simultaneously recorded using dual Doppler echocardiography in 45 AF patients (30 men; mean age, 69 ± 9 years). E/e' and T(E-e') were calculated and compared with the pulmonary capillary wedge pressure (PCWP), which was measured invasively. E/e' and T(E/e') correlated with PCWP (E/e', r=0.57, P<0.001; T(E-e'), r=0.77, P<0.001). Using receiver operating characteristic analysis, the optimal cut-off for T(E-e') was 34 ms (sensitivity, 95%; specificity, 88%) and that for E/e' was 14.6 (sensitivity, 50%; specificity, 84%) in order to predict >12-mmHg PCWP. When the combined cut-offs of T(E-e') >34 ms and E/e' >14.6 were used, the sensitivity and specificity of predicting elevated PCWP were improved to 100% and 88%, respectively. In AF patients, the simultaneous recording of E and e' using dual Doppler echocardiography and the analysis of T(E-e'), in addition to E/e', improved the accuracy of evaluation of LV filling pressure.

Pulmonary Capillary Wedge Pressure Augments Right Ventricular Pulsatile Loading

Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (R(PA)) and compliance (C(PA)) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load. Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the R(PA)-C(PA) relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent R(PA)-C(PA) hyperbolic (inverse) dependence, C(PA)=0.564/(0.047+R(PA)), with a near-constant resistance-compliance product (0.48±0.17 seconds). In the same patients, the systemic resistance-compliance product was highly variable. Severe pulmonary fibrosis (n=89) did not change the R(PA)-C(PA) relation. Increasing patient age led to a very small but statistically significant change in the relation. However, elevation of the pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly lowering C(PA) for any R(PA) and negatively correlating with the resistance-compliance product (P<0.0001). Pulmonary hypertension and pulmonary fibrosis do not significantly change the hyperbolic dependence between R(PA) and C(PA), and patient age has only minimal effects. This fixed relationship helps explain the difficulty of reducing total right ventricular afterload by therapies that have a modest impact on mean R(PA). Higher pulmonary capillary wedge pressure appears to enhance net right ventricular afterload by elevating pulsatile, relative to resistive, load and may contribute to right ventricular dysfunction.

Review of Ambulatory Pulmonary Artery Catheterization in the Management of Advanced Heart Failure

The use of pulmonary artery catheterization (PAC) has declined secondary to associated complications and lack of demonstrable efficacy in the inpatient setting. Few studies have been published on the use of PAC in nonacute heart failure (HF) patients. The purpose of this study was to review the use of PAC in guiding advanced therapy in nonacute ambulatory HF patients. A retrospective observational study assessing our group's practice pattern with regard to the use of PAC in 515 ambulatory HF patients, outcomes, and adverse events that resulted from its use was performed. A total of 159 ambulatory HF patients were referred for PAC; 7% underwent heart transplant, 6% had ventricular assist device (VAD) placement, 18% underwent inotropic therapy, and 48% had addition of therapy while 14% had subtraction of therapy. Adverse events occurred in 4% of ambulatory PAC. Patients who underwent heart transplant, VAD, or inotropic therapy had significantly elevated pulmonary capillary wedge pressures, mean pulmonary artery pressures, and depressed cardiac index. Patients selected for inotropic therapy also had significantly elevated right atrial pressures and depressed ejection fractions. PAC use safely guided medical therapy in more than half of the nonacute ambulatory patients.