Changes In Pulmonary Capillary Wedge Pressure Research Articles

Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction: The CAMEO-DAPA Trial.

Sodium-glucose cotransporter-2 inhibitors reduce risk of hospitalization for heart failure in patients who have heart failure with preserved ejection fraction (HFpEF), but the hemodynamic mechanisms underlying these benefits remain unclear. This study sought to determine whether treatment with dapagliflozin affects pulmonary capillary wedge pressure (PCWP) at rest and during exercise in patients with HFpEF. This was a single-center, double-blinded, randomized, placebo-controlled trial testing the effects of 10 mg of dapagliflozin once daily in patients with HFpEF. Patients with New York Heart Association class II or III heart failure, ejection fraction ≥50%, and elevated PCWP during exercise were recruited. Cardiac hemodynamics were measured at rest and during exercise using high-fidelity micromanometers at baseline and after 24 weeks of treatment. The primary end point was a change from baseline in rest and peak exercise PCWPs that incorporated both measurements, and was compared using a mixed-model likelihood ratio test. Key secondary end points included body weight and directly measured blood and plasma volumes. Expired gas analysis was performed evaluate oxygen transport in tandem with arterial lactate sampling. Among 38 patients completing baseline assessments (median age 68 years; 66% women; 71% obese), 37 completed the trial. Treatment with dapagliflozin resulted in reduction in the primary end point of change in PCWP at rest and during exercise at 24 weeks relative to treatment with placebo (likelihood ratio test for overall changes in PCWP; P<0.001), with lower PCWP at rest (estimated treatment difference [ETD], -3.5 mm Hg [95% CI, -6.6 to -0.4]; P=0.029) and maximal exercise (ETD, -5.7 mm Hg [95% CI, -10.8 to -0.7]; P=0.027). Body weight was reduced with dapagliflozin (ETD, -3.5 kg [95% CI, -5.9 to -1.1]; P=0.006), as was plasma volume (ETD, -285 mL [95% CI, -510 to -60]; P=0.014), but there was no significant effect on red blood cell volume. There were no differences in oxygen consumption at 20-W or peak exercise, but dapagliflozin decreased arterial lactate at 20 W (-0.70 ± 0.77 versus 0.37 ± 1.29 mM; P=0.006). In patients with HFpEF, treatment with dapagliflozin reduces resting and exercise PCWP, along with the favorable effects on plasma volume and body weight. These findings provide new insight into the hemodynamic mechanisms of benefit with sodium-glucose cotransporter-2 inhibitors in HFpEF. URL: https://www. gov; Unique identifier: NCT04730947.

Catheter ablation in atrial fibrillation and heart failure with preserved ejection fraction improves peak pulmonary capillary wedge pressure, exercise capacity and quality of life: RCT STALL HFpEF

Abstract Introduction Atrial fibrillation (AF) frequently accompanies heart failure with preserved ejection fraction (HFpEF). AF exacerbates HFpEF through adverse haemodynamic effects. In turn, HFpEF promotes AF through adverse left atrial remodelling. Observational data suggest sinus rhythm restoration improves outcomes in patients with AF and HFpEF. However, there are no randomised data examining the effects of rhythm control with catheter-based AF ablation on HFpEF outcomes. Purpose To compare the effects of AF ablation versus usual medical therapy on markers of HFpEF severity, including exercise haemodynamics, natriuretic peptide levels and patient symptoms. Methods Patients with symptomatic AF and HFpEF underwent exercise right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET). HFpEF diagnosis was based on left ventricular ejection fraction (LVEF) ≥50%, elevated natriuretic peptide and echocardiographic diastolic impairment. HFpEF was confirmed on exercise RHC based on peak exercise pulmonary capillary wedge pressure (PCWP) of ≥25mmHg. Patients were randomised to AF ablation versus medical therapy, with investigations repeated at 6 months. The primary outcome was change in PCWP on follow-up. Results 31 patients aged 66.1±7.5 years were randomized to AF ablation (16) versus medical therapy (15), with 51.6% female and 80.6% persistent AF. Baseline characteristics were comparable across groups. Paired analyses of ablation cohort showed significant reductions in peak PCWP (29.6±3.7 vs 25.9±4.6 mmHg, p&amp;lt;0.01), PCWP indexed for workload (39.0±57.9 vs 33.0±50.5 mmHg/W/kg, p&amp;lt;0.01), and BNP (146.2±80.5 vs 82.2±75.4 pg/mL, p=0.01); and increased resting cardiac output (4.6±0.9 vs 5.6±1.2 L/min, p=0.01), peak cardiac output (9.6±4.2 vs 10.4±3.7 L/min, p=0.02), peak (30s averaged) VO2 (1875.1±759.2 vs 2193.7±878.1 mL/min, p&amp;lt;0.01), peak absolute VO2 (1937.3±739.3 vs 2216.3±861.9 mL/min, p&amp;lt;0.01), peak (30s averaged) relative VO2 (19.4±5.9 vs 22.9±7.4 ml/kg/min) and peak workload (162.0±81.1 vs 184.4±83.4 W, p&amp;lt;0.01). Quality of life scores improved: AFEQT (45.3±20.9 vs 75±20.7, p&amp;lt;0.01) and MLHF (53±23.3 vs 17.5±22.8, p&amp;lt;0.01). Reversal of HFpEF by PCWP criteria occurred in 31.2% following AF ablation, and 50% among those free from arrhythmia recurrence. In the medical arm, there were no significant differences in RHC, CPET, and natriuretic peptide outcomes on follow-up versus baseline. Repeated measures mixed ANOVA testing showed significant time-randomisation interaction on peak VO2, absolute peak VO2, peak relative VO2, AFEQT/ MLHF scores, suggesting that significant improvements in these parameters were related to AF ablation. Conclusion In patients with concomitant AF and HFpEF, AF ablation improves invasive exercise haemodynamic parameters, increases exercise capacity, and enhances quality of life. Successful AF ablation may reverse the clinical syndrome of HFpEF in a subset of cases. Funding Acknowledgement Type of funding sources: None.

Lung ultrasound predicts left-sided filling pressures in patients with cardiogenic shock admitted to the cardiac intensive care unit

Abstract Background Left and right filling pressures, as well as cardiac output, are key targets in optimising treatment of cardiogenic shock (CS). Invasive pulmonary artery catheters can provide these data but are associated with complications and are not available in all hospital settings. Lung ultrasound (LUS) can detect pulmonary congestion in patients with heart failure (HF) and may be an alternative to invasive monitoring. We assessed the correlation between LUS score and invasive haemodynamic parameters in patients with CS admitted to the cardiac intensive care unit (CICU) of a North American cardiac centre. Methods We prospectively evaluated consecutive patients who underwent pulmonary artery catheter insertion in the CICU. Haemodynamic parameters including right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were measured and cardiac output (CO) was calculated using the thermodilution method. This was immediately followed by an 8-zones LUS done by a critical care cardiologist who was blinded to the invasive hemodynamic measurements. The LUS score was calculated by counting the total number of B-lines in all 8 zones, with a higher score indicating greater congestion. Correlations between LUS score and hemodynamic parameters were evaluated using Pearson's correlation. Results Ninety-six measurements from 60 patients were included, aged 58±14 years with 27% female. The most common diagnosis at admission was cardiogenic shock, followed by acute myocardial infarction and HF exacerbation. Most patients were at SCAI stages C and D at the time of assessment. The mean number of B-lines at LUS was 10.1±8.2. Mean RAP was 8.5±4.6 mmHg, PCWP 16.2±6.3 mmHg and CO of 5.0±1.8 L/min. The total number of B-lines was correlated with PCWP (r=0.66, P&amp;lt;0.001, see Figure 1), RAP (r=0.26, P&amp;lt;0.001) and cardiac output (r=−0.23, p=0.02). Due to the correlation of B-lines in LUS with PCWP, we then evaluated the area under the ROC of the LUS to identify patients with PCWP ≥15 mmHg. The number of positive zones (≥3 B-lines) showed an AUC of 0.81 (0.72–0.89), P&amp;lt;0.001. In 36 patients, we had repeated measurement with more than 12 hours apart. The delta change in PCWP was correlated with delta change in the number of B-lines (r=0.59, P&amp;lt;0.001). Conclusion Elevated LUS score in patients with CS is associated with worse invasively-measured LV filling pressures, but less so with RAP or CO. LUS can serve as a useful adjunct to the clinical assessment of patients with CS who do not receive invasive hemodynamic monitoring, either at a single timepoint or to detect changes in clinical status over time, to guide ongoing management. Funding Acknowledgement Type of funding sources: None.

Trimetazidine in heart failure with preserved ejection fracton: a randomized, double-blind cross-over trial

Abstract Introduction Impaired myocardial mitochondrial function plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and there is evidence indicative of a causal relationship between observed impaired energy homeostasis and diastolic dysfunction. Improvement of mitochondrial function with metabolism-modulating drugs may be a promising novel therapeutic approach in HFpEF. Trimetazidine – a fatty acid oxidation inhibitor – shifts mitochondrial metabolism towards glucose oxidation, which results in higher mitochondrial oxygen efficiency. In this study we investigated whether trimetazidine improves diastolic function during exercise in HFpEF by improving the myocardial energy homeostasis. Methods The DoPING-HFpEF trial was a phase II single-center, double-blind, placebo-controlled, randomized cross-over trial. The study consisted of two treatment periods of three months separated by a 2-week wash-out period (Figure 1). Patients were treated with placebo or trimetazidine three times a day (or twice daily in case of an impaired kidney function). The primary endpoint was change in pulmonary capillary wedge pressure (PCWP) measured with right heart catheterization at multiple stages of exercise. Secondary endpoint was change in phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance (MR) spectroscopy. Additional exploratory endpoints were 6-minute-walking-distance, diastolic and systolic parameters measured with echocardiography or cardiac MR, NT-proBNP levels, and quality of life. Results Twenty-five HFpEF patients were included and completed the trial, 80% of which were included based on previously established elevated (exercise) PCWP, and 20% were included based on diastolic dysfunction grade ≥II on echocardiography and elevated NT-proBNP levels. There was no effect on the primary outcome PCWP at multiple levels of exercise, with an average change in PCWP of 0±4 (SD) mmHg (Figure 2A, P=0.97). Myocardial PCr/ATP in the trimetazidine arm was similar to placebo (Figure 2B, P=0.08). There was no change by trimetazidine in the exploratory parameters 6-minute walking distance, NT-proBNP, overall quality of life, or other parameters for diastolic function measured with echocardiography and cardiac MR. There was no indication of period or cross over effect. Conclusion Trimetazidine did not improve diastolic function or myocardial energy homeostasis in patients with HFpEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation (DHF) and “Out-of-the-Box” grant from the Amsterdam Cardiovascular Sciences (ACS) Institute, Amsterdam, The Netherlands.

Estimation of Changes in Intracardiac Hemodynamics Using Wearable Seismocardiography and Machine Learning in Patients With Heart Failure: A Feasibility Study.

Tracking changes in hemodynamic congestion and the consequent proactive readjustment of treatment has shown efficacy in reducing hospitalizations for patients with heart failure (HF). However, the cost-prohibitive nature of these invasive sensing systems precludes their usage in the large patient population affected by HF. The objective of this research is to estimate the changes in pulmonary artery mean pressure (PAM) and pulmonary capillary wedge pressure (PCWP) following vasodilator infusion during right heart catheterization (RHC), using changes in simultaneously recorded wearable seismocardiogram (SCG) signals captured with a small wearable patch. A total of 20 patients with HF (20% women, median age 55 (interquartile range (IQR), 44-64) years, ejection fraction 24 (IQR, 16-43)) were fitted with a wearable sensing patch and underwent RHC with vasodilator challenge. We divided the dataset randomly into a training-testing set (n = 15) and a separate validation set (n = 5). We developed globalized (population) regression models to estimate changes in PAM and PCWP from the changes in simultaneously recorded SCG. The regression model estimated both pressures with good accuracies: root-mean-square-error (RMSE) of 2.5 mmHg and R2 of 0.83 for estimating changes in PAM, and RMSE of 1.9 mmHg and R2 of 0.93 for estimating changes in PCWP for the training-testing set, and RMSE of 2.7 mmHg and R2 of 0.81 for estimating changes in PAM, and RMSE of 2.9 mmHg and R2 of 0.95 for estimating changes in PCWP for the validation set respectively. Changes in wearable SCG signals may be used to track acute changes in intracardiac hemodynamics in patients with HF. This method holds promise in tracking longitudinal changes in hemodynamic congestion in hemodynamically-guided remote home monitoring and treatment for patients with HF.

Resting and exercise hemodynamic determinants of daily activity measured by accelerometer in stable heart failure patients

Abstract Background Patient-worn accelerometer is increasingly used in patients with heart failure and reduced ejection fraction (HFrEF) to assess daily activity and and as surrogate endpoint. We examined the association between cardiac physiology and daily activity by patient-worn accelerometer recordings in stable HFrEF patients. Methods In this descriptive study, physical average daily accelerometer units (PADA) and total average daily accelerometer unit (TADA) were assessed by a accelerometer recordings. Sixty three stable ambulatory patients with HFrEF, mainly men (92%), mean age 58±10 years, and ejection-fraction 26±4% underwent hemodynamic exercise testing, and accelerometry (Table 1). Patients were divided by PADA in a low and high activity level groups based on counts per minute physical activity. Results Patients in the low activity group were older and more frequently treated with diuretics. At rest, the low activity group was characterized by a lower cardiac index (CI) (2.2±0.4 vs. 2.4±0.4 l/min/m2, p=0.01), Stroke volume (SV) (70±19 vs. 81±17 ml, p=0.02) but not pulmonary capillary wedge pressure (PCWP) (12±5 vs. 11±5 mmHg, p=0.3) (Figure 1). Low activity group reached a lower CI (4.8±1.7 vs. 6.6±1.7 l/min/m2, p&amp;lt;0.001) and SV (94±32 vs. 121±29 ml, p&amp;lt;0.001), but not in PCWP (31±12 vs. 27±8 mmHg, p=0.2) or arterial-venous O2 content difference (A-VO2 diff) (13.00±2.32 vs. 12.96±1.65 ml O2/dl, p=0.9) at peak exercise. The attenuated increase was associated with attenuated increase in SV rther than increase in heart rate (42±23 vs. 52±21 bpm, p=0.07). Finally, CI at peak exercise was the only independent variable associated with PADA after adjusting for age, gender, and BMI (p&amp;lt;0.0001). The PADA and TADA were associated to functional assessments using Kansas City Cardiomyopathy Questionnaire, but not with New York Heart Association class or N-terminal pro brain natriuretic peptide (NT-proBNP) (Table 1). Conclusion Accelerometer-assessed activity in patients with HFrEF are associated with impairments in LV performance, SV reserve and cardiac output during exercise, to a greater extent than changes in arterial-venous O2 content difference or pulmonary vascular pressures. Accelerometer data may provide information about the functional status that we do not nessecary find in the widely used tools in both research and daily clinical practice. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the Danish Heart Foundation [grant numbers 17-R116-A7714-22076, 18-R124-A8573-22107]; Steno Diabetes Center Odense, Denmark [grant number 3363] and A.P. Møller Foundation for the Advancement of Medical Science [grant number 17-L-0339]. Table 1. Baseline and regression analysisFigure 1. Change in PCWP and CI by exercise

Hemodynamic changes during transcatheter atrial septal defect closure predict midterm heart failure deterioration in adults.

To investigate whether hemodynamic changes during balloon occlusion test (BOT) predict future heart failure (HF) deterioration after transcatheter atrial septal defect closure (tASD-closure). Midterm HF deterioration can sometimes occur after tASD-closure in adults. Whether hemodynamic changes during tASD-closure can help identify patients at risk is unknown. This prospective observational study enrolled 86 consecutive adult patients who underwent tASD-closure. Hemodynamic parameters, including pulmonary capillary wedge pressure (PCWP), were measured at baseline, during BOT, and after tASD-closure. The changes in PCWP during BOT and after tASD-closure were defined as ΔPCWP (Occ-Pre) and ΔPCWP (Post-Pre), respectively. Clinical parameters were evaluated before tASD-closure and during the 3-month follow-up. We assessed the occurrence of HF deterioration (HF requiring hospitalization or additional diuretics) during a 2-year follow-up period and categorized patients into HF (+) and HF (-) groups accordingly. The aforementioned parameters were compared between groups. Midterm HF deterioration occurred in 12 patients (13.9%). Compared to the HF (-) group, the HF (+) group presented a significantly higher ΔPCWP (Occ-Pre) (9.5 ± 4.4 mmHg vs. 3.0 ± 3.3 mmHg; p < 0.001) and ΔPCWP (Post-Pre) (4.0 ± 2.8 mmHg vs. 0.6 ± 1.8 mmHg; p=0.004). Receiver operating characteristic curve analysis showed that the ΔPCWP (Occ-Pre) cutoff value of 5.5 mmHg had excellent ability to predict HF deterioration (Area under the curve 0.886 [0.779-0.993], p < 0.001; sensitivity 0.917, specificity 0.824). Increases in PCWP during BOT predict midterm HF deterioration after tASD-closure. Close surveillance may be needed in patients with a ΔPCWP (Occ-Pre) >5 mmHg.

The diagnostic value of passive leg raise during right heart catheterization in diagnosing heart failure with preserved ejection fraction

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a frequent and disabling disease, but can be difficult to diagnose. Due to limited sensitivity of non-invasive evaluation of left ventricular (LV) diastolic dysfunction, invasive measurement may be warranted. The gold standard for diagnosing HFpEF is invasive measurement of LV end-diastolic pressure or its surrogate pulmonary capillary wedge pressure (PCWP). In case of normal LV filling pressures at rest (PCWP@rest &amp;lt;16 mmHg), patients should undergo stress testing to unmask occult HFpEF (early HFpEF if PCWP@exercise ≥25mmHg). Performing exercise during a right heart catheterization is time-consuming and logistically challenging. Passive leg raise increases venous return and can lead to an abnormal increase in LV filling pressures in case of diastolic dysfunction. Whether this leg raise maneuver (PCWP@legraise) can be used as an accurate method to diagnose or exclude HFpEF and what cut-off values should be used is unknown. Purpose To assess the diagnostic value of PCWP@legraise during right heart catheterization for HFpEF. Methods We reviewed all consecutive patients who received a diagnostic right heart catheterization with PCWP-measurements at rest, passive leg raise and during exercise (minimally &amp;gt;40% peak VO2) between 2017 and 2020 in a tertiary medical center (n=124). Zero reference point was defined mid-thorax. PCWP was measured end-expiratory mid A-wave. Patients with insufficient data (n=17), uninterpretable tracings (n=13) or PCWP@rest &amp;gt;16 mmHg were excluded (n=19). The diagnostic value of PCWP@legraise was compared to the gold standard for HFpEF (PCWP@exercise). Results We analyzed 75 patients, with a mean age of 58 (±16) years, female (60%), mean BMI 27.8 (±5.5). HFpEF was diagnosed in 47% of the cases, non-HFpEF existed of pulmonary arterial hypertension (23%), chronic thrombo-embolic disease (15%) or other (15%). Figure 1A shows PCWP@rest, PCWP@legraise, PCWP@exercise for HFpEF and non-HFpEF. The diagnostic performance of PCWP@legraise was higher than PCWP@rest (Figure 1B; AUC 0.83 vs 0.75). PCWP@legraise ≥22 mmHg had a specificity of 100% and a positive predictive value of 100% for diagnosing HFpEF and could be used as a cut-off for diagnosing HFpEF. PCWP@legraise of ≥13 mmHg had a sensitivity of 98% and a negative predictive value of 93%, and could be used as a cut-off for excluding HFpEF. If these cut-offs were used to refute or diagnose HFpEF, 17 patients (23%) could have been differed from exercise during right heart catheterization. The change in PCWP due to passive leg raise was of lower diagnostic value than the absolute value of PCWP@legraise. Conclusion In our cohort, the leg raise maneuver is of diagnostic value. With the proposed PCWP@legraise criteria for HFpEF - validated against the gold standard (PCWP@exercise) - the exercise could have been omitted in almost a quarter of the cases. More (external) validation is warranted. Figure 1 Funding Acknowledgement Type of funding source: None

Longitudinal Strain and Strain Rate for Estimating Left Ventricular Filling Pressure in Heart Transplant Recipients

Traditional parameters have limited value to estimate left ventricular filling pressure (LVFP) in orthotropic heart transplant (OHT) recipients. We hypothesized that global longitudinal strain (GLS), diastolic, and systolic strain rate (SR) would be depressed in OHT recipients with elevated LVFP and could overcome the limitations of traditional parameters. We studied consecutively OHT patients at the time of endomyocardial biopsies and retrospectively pretransplantation studies conforming to the same protocol. Comprehensive echocardiography with strain measurements was performed. Results were compared with pulmonary capillary wedge pressure (PCWP) obtained from right heart catheterization that was performed just after the echocardiography study. In all, 74 studies were performed in 50 OHT recipients. Mean PWCP was 11.8 ± 4.3 mm Hg (range: 4 to 25 mm Hg). Several parameters, but not left atrial volume index, mitral inflow velocities, annular velocities, and their ratio (E/e'), were different between studies with normal (n = 47) and elevated PCWP (n = 27). Area Under Curve for GLS (0.932*), E/e'SR (0.849*), and systolic SR (0.848*) (*p <0.0001) were more accurate than traditional parameters for predicting PCWP>12 mm Hg. GLS, systolic SR and E/e'SR remained accurate regardless of LV ejection fraction and allograft vasculopathy. Meanwhile, E/e' was accurate to predict PWCP in native failing hearts before transplantation. Changes in GLS and E/e'SR tracked accurately changes in PCWP. In conclusion, traditional indices of diastolic function perform poorly in OHT recipients, whereas GLS and E/e'SR provide reliable means of LVFP, irrespective of ejection fraction and allograft vasculopathy. These parameters also track reasonably well the changes in LVFP.

Usefulness of Diastolic Strain Measurements in Predicting Elevated Left Ventricular Filling Pressure and Risk of Rejection or Coronary Artery Vasculopathy in Pediatric Heart Transplant Recipients

In pediatric heart transplant recipients, elevated pulmonary capillary wedge pressure (PCWP) is associated with rejection and coronary artery vasculopathy. This study aimed to evaluate which echocardiographic parameters track changes in PCWP and predict adverse outcomes (rejection or coronary artery vasculopathy). This prospective single-center study enrolled 49 patients (median 11.4 years old, interquartile range 7.4 to 16.5) at time of cardiac catheterization and echocardiography. Median follow-up was 2.4 years (range 1.2 to 3.1 years), with serial testing per clinical protocol. Ratio of early mitral inflow to annular velocity (E/E'), left atrial (LA) distensibility, peak LA systolic strain, E/left ventricular (LV) diastolic strain, and E/LV diastolic strain rate were measured from echocardiograms. Increase in PCWP ≥3 mm Hg was associated with changes in LA distensibility, E/E', and E/LV diastolic strain, with highest area under the receiver operating characteristic curve for E/LV diastolic strain (0.76). In 9 patients who subsequently developed rejection or coronary artery vasculopathy, E/LV diastolic strain rate at baseline differed from patients without events (median 57.0 vs 43.6, p = 0.02). On serial studies, only change in LV ejection fraction differed in patients with events (median -10% vs -1%, p = 0.01); decrease in LV ejection fraction of -19% had a specificity of 100% and sensitivity of 44%. In conclusion, LV diastolic strain and strain rate measurements can track changes in PCWP and identify patients at risk for subsequent rejection or coronary artery vasculopathy. Further studies are necessary to confirm these data in a larger cohort.

Relationships Between Biomarkers and Left Ventricular Filling Pressures at Rest and During Exercise in Patients After Myocardial Infarction

BackgroundIncreased pulmonary capillary wedge pressure (PCWP) is an independent prognostic predictor after myocardial infarction (MI), but PCWP is difficult to assess noninvasively in subjects with preserved ejection fraction (EF). We hypothesized that biomarkers would provide information regarding PCWP at rest and during exercise in subjects with preserved EF after MI. Methods and ResultsSeventy-four subjects with EF >45% and recent MI underwent right heart catheterization at rest and during a symptom-limited semisupine cycle exercise test with simultaneous echocardiography. Plasma samples were collected at rest for assessment of midregional pro–A-type natriuretic peptide (MR-proANP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), copeptin, and midregional pro-adrenomedullin (MR-proADM). Plasma levels of MR-proANP and PCWP were associated at rest (r = 0.33; P = .002) and peak exercise (r = 0.35; P = .002) as well as with changes in PCWP (r = 0.26; P = .03). Plasma levels of NT-proBNP and PCWP were weakly associated at rest (r = 0.23; P = .03) and peak exercise (r = 0.28; P = .02) but not with changes in PCWP (r = 0.20; P = .09). In a multivariable analysis, plasma levels of MR-proANP remained associated with rest and exercise PCWP (P < .01), whereas NT-proBNP did not. Plasma levels of Gal-3, copeptin, and MR-proADM were not associated with PCWP at rest or peak exercise. ConclusionsIn subjects recovering from an acute MI with preserved EF, plasma levels of natriuretic peptides, particularly MR-proANP, are associated with filling pressures at rest and during exercise.

Exercise-induced changes in left ventricular filling pressure after myocardial infarction assessed with simultaneous right heart catheterization and Doppler echocardiography

To assess whether changes in E/e´ (the ratio between peak early mitral inflow velocity (E) and peak early mitral annulus velocity (e´)) during exercise reflect changes in filling pressure in patients with a recent myocardial infarction (MI) and mild to moderate diastolic dysfunction at rest. A low E/e´ ratio is associated with low filling pressures while a high E/e´ ratio is associated with high filling pressures. In the intermediate range of E/e´ guidelines suggest additional measurements during exercise in order to determine filling pressures. Sixty-one patients with a recent MI and left ventricular ejection fraction (LVEF) ≥ 45%, left atrium (LA)>34 ml/m(2) and E/e´ between 8 and 15, underwent simultaneous right heart catheterization and Doppler echocardiography during a symptom limited semi supine cycle exercise test. E velocity increased from 75 ± 16 to 139 ± 27 cm/s and e´ increased from 7.1 ± 1.4 to 16.1 ± 3.6 cm/s with exercise. Thus, E/e´ decreased from 10.5 ± 1.7 to 9.3 ± 2.3 while pulmonary capillary wedge pressure (PCWP) increased from 13 ± 4 to 33 ± 8 mmHg. There was no correlation between LV filling pressure and E/e´ at rest, at 4 METS, at peak exercise or 5 min after termination of exercise. Neither was there any correlation between changes in PCWP and changes in E/e´. For post-MI patients with resting E/e´ in the intermediate range changes in E/e´ with physical exercise does not reflect changes in LV filling pressures.

Intravenous levosimendan vs. dobutamine in acute decompensated heart failure patients on beta‐blockers

AimsThe aim of this study is to compare the effects of a 24 h intravenous infusion of levosimendan and a 48 h infusion of dobutamine on invasive haemodynamics in patients with acutely decompensated chronic NYHA class III–IV heart failure. All patients were receiving optimal oral therapy including a β-blocker.Methods and resultsThis was a multinational, randomized, double-blind, phase IV study in 60 patients; follow-up was 1 month. There was a significant increase in cardiac index and a significant decrease in pulmonary capillary wedge pressure (PCWP) at 24 and 48 h for both dobutamine and levosimendan. The improvement in cardiac index with levosimendan was not significantly different from dobutamine at 24 h (P = 0.07), but became significant at 48 h (0.44 ± 0.56 vs. 0.66 ± 0.63 L/min/m2; P = 0.04). At 24 h, the reduction in the mean change in PCWP from baseline was similar for levosimendan and dobutamine, however, at 48 h the difference was more marked for levosimendan (−3.6 ± 7.6 vs. −8.3 ± 6.7 mmHg; P = 0.02). No difference was observed between the groups for change in NYHA class, β-blocker use, hospitalizations, treatment discontinuations or rescue medication use. Reduction in B-type natriuretic peptide (BNP) was significantly greater with levosimendan at 48 h (P = 0.03). According to physician's assessment, the improvement in fatigue (P = 0.01) and dyspnoea (P = 0.04) was in favour of dobutamine treatment, and hypotension was significantly more frequent with levosimendan (P = 0.007). No increase in atrial fibrillation or ventricular tachycardia was seen in either group.ConclusionA 24 h levosimendan infusion achieved haemodynamic and neurohormonal improvement that was at least comparable at 24 h and superior at 48 h to a 48 h dobutamine infusion.

The Relationship of Right- and Left-Sided Filling Pressures in Patients With Heart Failure and a Preserved Ejection Fraction

Although right-sided filling pressures often mirror left-sided filling pressures in systolic heart failure, it is not known whether a similar relationship exists in heart failure with preserved ejection fraction. Eleven subjects with heart failure with preserved ejection fraction underwent right heart catheterization at rest and under loading conditions manipulated by lower body negative pressure and saline infusion. Right atrial pressure (RAP) was classified as elevated when >or=10 mm Hg and pulmonary capillary wedge pressure (PCWP) when >or=22 mm Hg. If both the RAP and the PCWP were elevated or both not elevated, they were classified as concordant; otherwise, they were classified as discordant. Correlation of RAP and PCWP was determined by a repeated measures model. Among 66 paired measurements of RAP and PCWP, 44 (67%) had a low RAP and PCWP and 8 (12%) a high RAP and PCWP, yielding a concordance rate of 79%. In a sensitivity analysis performed by varying the definition of elevated RAP (from 8 to 12 mm Hg) and PCWP (from 15 to 25 mm Hg), the mean+/-SD concordance of RAP and PCWP was 76+/-10%. The correlation coefficient of RAP and PCWP for the overall cohort was r=0.86 (P<0.0001). Right-sided filling pressures often reflect left-sided filling pressures in heart failure with preserved ejection fraction, supporting the role of estimation of jugular venous pressure to assess volume status in this condition.

Pathophysiological changes of dogs with open abdominal injury and seawater immersion-induced acute heart failure

Objective:To observe the pathophysiological changes of dogs with open abdominal injury and seawater immersion-induced acute heart failure.Methods:Adult mongrel dogs were randomly divided into open abdominal injury+seawater immersion group(group A,n=8) and simple open abdominal injury group(group B,n=8).The cardiac rhythm,heart rate,systolic pressure,diastolic pressure,mean arterial pressure,pulmonary wedge pressure,central venous pressure,cardiac output,heart index,rennin,B-type brain natriuretic peptide(BNP),other relevant parameters and death rate were observed before and after open abdominal injury,during 2h seawater immersion,and at different time points after getting out of the water.The left ventiricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),stroke volumes(SV),and left ventricular ejection fraction(LVEF) were measured before and 4 h after injury by ultrasonic cardiogram.Results:The mean arterial pressure decreased significantly in group A from 5 min after injury to the end of the ovservation(P0.05,P0.01),and that of group B had no measurable changes.The pulmonary capillary wedge pressure(PAWP) increased significantly;the central venous pressure,cardiac output,and cardiac index decreased gradually,and continued to decrease after putting out of water,which were significantly different from those of group B(P0.05,P0.01).Group B had no measurable changes in PAWP,central venous pressure,cardiac output,and cardiac index before and after abdominal injury.The blood rennin and BNP levels were significantly increased in group A(P0.05,P0.01)and had no significant changes in group B.Conclusion:Prominent pathophysiological changes occur in rats with open abdominal injury and seawater immersion-induced acute heart failure.

Effects of istaroxime on diastolic stiffness in acute heart failure syndromes: Results from the Hemodynamic, Ech ocardiographic, and Neu rohormonal Effects of Istaroxime, a Novel Intravenous Inotropic and Lusitropic Agent: a Randomi zed C ontrolled Trial in Patients Hospitalized with Heart Failure (HORIZON-HF) trial

Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of the Na+/K+ adenosine triphosphatase and stimulation of sarcoplasmic reticulum calcium adenosine triphosphatase activity. We analyzed data from HORIZON-HF, a randomized, controlled trial evaluating the short-term effects of istaroxime in patients hospitalized with heart failure and left ventricular ejection fraction < or = 35% to test the hypothesis that istaroxime improves diastolic stiffness in acute heart failure syndrome. One hundred twenty patients were randomized 3:1 (istaroxime/placebo) to a continuous 6-hour infusion of 1 of 3 doses of istaroxime or placebo. All patients underwent pulmonary artery catheterization and comprehensive 2-dimensional/Doppler and tissue Doppler echocardiography at baseline and at the end of the 6-hour infusion. We quantified diastolic stiffness using pressure-volume analysis and tissue Doppler imaging of the lateral mitral annulus (E'). Baseline characteristics were similar among all groups, with mean age 55 +/- 11 years, 88% men, left ventricular ejection fraction 27% +/- 7%, systolic blood pressure (SBP) 116 +/- 13 mm Hg, and pulmonary capillary wedge pressure (PCWP) 25 +/- 5 mm Hg. Istaroxime administration resulted in an increase in E' velocities, whereas there was a decrease in E' in the placebo group (P = .048 between groups). On pressure-volume analysis, istaroxime decreased end-diastolic elastance (P = .0001). On multivariate analysis, increasing doses of istaroxime increased E' velocity (P = .043) and E-wave deceleration time (P = .001), and decreased E/E' ratio (P = .047), after controlling for age, sex, baseline ejection fraction, change in PCWP, and change in SBP. Istaroxime decreases PCWP, increases SBP, and decreases diastolic stiffness in patients with acute heart failure syndrome.

Left Ventricular Filling Pressure Estimation at Rest and During Exercise in Patients With Severe Aortic Valve Stenosis: Comparison of Echocardiographic and Invasive Measurements

The Doppler index of left ventricular (LV) filling (E/e') is recognized as a noninvasive measure for LV filling pressure at rest but has also been suggested as a reliable measure of exercise-induced changes. The aim of this study was to investigate changes in LV filling pressure, measured invasively as pulmonary capillary wedge pressure (PCWP), at rest and during exercise to describe the relation with E/e' in patients with severe aortic stenosis. Twenty-eight patients with an aortic valve areas<1 cm(2) performed a multistage supine bicycle exercise test until exhaustion. PCWP, E/e'(septal), and E/e'(lateral) were determined simultaneously by echocardiography at rest and at maximal tolerated workload. PCWP increased significantly from 18+/-8 mm Hg at rest to 39+/-10 mm Hg at peak exercise (P < .0001). E, e'(septal), and e'(lateral) increased with exercise, whereas E/e'(septal) remained unchanged (19+/-6 vs 19+/-6; P=NS), and only minimal changes were observed in E/e'(lateral) (14+/-4 vs 15+/-4; P=.05). E/e'(septal) and E/e'(lateral) were significantly correlated with PCWP at rest (r=0.72, P < .0001, and r=0.67, P < .0001, respectively) as well as at peak exercise (r=0.66, P=.0003, and r=0.47, P=.02, respectively), with nearly similar slopes of the linear regression lines. The intercepts, however, increased by 18 mm Hg (P=.01) and by 19 mm Hg (P=.01) at peak exercise, respectively. Changes in E/e'(septal) and E/e'(lateral) were not related to changes in PCWP with exercise (P=NS). Instead, the ratio of E velocity during exercise to e'(septal) at rest (E(exercise)/e'(septal, rest)) was correlated with PCWP during exercise (r=0.61, P=.001), and furthermore, E(exercise)-E(rest)/e'(septal, rest) was related to changes in PCWP (r=0.45, P=.02). The results for the lateral side were r=0.50 (P=.01) and r=0.44 (P=.03), respectively. E/e' is well correlated with PCWP at rest. However, E/e' cannot be used to detect exercise-induced changes in PCWP in patients with severe aortic stenosis. Using the ratio of E during exercise to e' at rest may result in a better estimate of the increase in PCWP during exercise.

Tissue Doppler Imaging in the Estimation of Intracardiac Filling Pressure in Decompensated Patients With Advanced Systolic Heart Failure

The ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/Ea) has been correlated with pulmonary capillary wedge pressure (PCWP) in a wide variety of cardiac conditions. The objective of this study was to determine the reliability of mitral E/Ea for predicting PCWP in patients admitted for advanced decompensated heart failure. Prospective consecutive patients with advanced decompensated heart failure (ejection fraction < or =30%, New York Heart Association class III to IV symptoms) underwent simultaneous echocardiographic and hemodynamic evaluation on admission and after 48 hours of intensive medical therapy. A total of 106 patients were included (mean age, 57+/-12 years; ejection fraction, 24+/-8%; PCWP, 21+/-7 mm Hg; mitral E/Ea ratio, 20+/-12). No correlation was found between mitral E/Ea ratio and PCWP, particularly in those with larger left ventricular volumes, more impaired cardiac indexes, and the presence of cardiac resynchronization therapy. Overall, the mitral E/Ea ratio was similar among patients with PCWP >18 and < or =18 mm Hg, and sensitivity and specificity for mitral E/Ea ratio >15 to identify a PCWP >18 mm Hg were 66% and 50%, respectively. Contrary to prior reports, we did not observe any direct association between changes in PCWP and changes in mitral E/Ea ratio. In decompensated patients with advanced systolic heart failure, tissue Doppler-derived mitral E/Ea ratio may not be as reliable in predicting intracardiac filling pressures, particularly in those with larger LV volumes, more impaired cardiac indices, and the presence of cardiac resynchronization therapy.

Echocardiographic Predictors of Change in Left Ventricular Diastolic Pressure in Heart Failure Patients Receiving Nesiritide

To evaluate the usefulness of currently accepted echocardiographic parameters of diastolic function to assess the acute change in left ventricular end-diastolic pressure (LVEDP) following the administration of nesiritide in a heart failure population. In 25 heart failure patients (15 with systolic dysfunction, 10 with preserved ejection fraction [EF]), Doppler echocardiography, right and left heart catheterization, and invasive biventricular pressure hemodynamics were obtained at baseline and 30 minutes after nesiritide infusion. Twenty-four patients had sufficient echocardiographic images for analysis. The mean age was 60 +/- 11 years, 48% were male, 56% had coronary artery disease, and 64% had hypertension. Right ventricular systolic pressure (RVSP) had the highest correlation with LV filling pressure: pulmonary capillary wedge pressure (PCWP), pre-A wave LV, and LVEDP (r = 0.66, P = 0.0009; r = 0.63, P = 0.002; r = 0.72, P = 0.0002, respectively). Following nesiritide administration, the mean PCWP decreased from 17.1 +/- 7.8 mmHg at baseline to 9.6 +/- 6.2 mmHg (P < 0.001). Change in RVSP had the highest correlation with change in PCWP (r =-0.67, P = 0.10) and change in LVEDP (r =-0.71, P = 0.07). Echocardiographic parameters are frequently assessed in attempts to estimate left heart diastolic pressures. In heart failure patients, RVSP appears to be the best predictor of LVEDP, outperforming tissue Doppler E/E'. RVSP was found to be the best echocardiographic predictor of change in LV filling pressure with intravenous vasodilator therapy in heart failure patients. RVSP may provide a noninvasive means of assessing response to cardiac therapy.

Doppler Estimation of Left Ventricular Filling Pressures in Patients With Mitral Valve Disease

Conventional Doppler measurements have limitations in the prediction of left atrial pressure (LAP) in patients with mitral valve disease (MVD), given the confounding effect of valve area, left ventricular (LV) relaxation, and stiffness. However, the time interval between the onset of early diastolic mitral inflow velocity (E) and annular early diastolic velocity (Ea) by tissue Doppler imaging (TDI), T(E-Ea), which is well related to the time constant of LV relaxation (tau) in canine and clinical studies, is not subject to these variables. We therefore undertook this study to test its usefulness in a patient population. Two-dimensional Doppler and TDI echocardiography were performed simultaneously with right-heart catheterization in 51 consecutive patients (mean+/-SD age, 64+/-11 years) with MVD: 35 with moderately severe to severe mitral regurgitation (MR) and 16 with moderate to severe mitral stenosis (MS). Among several Doppler measurements, only the mitral E/A ratio, isovolumetric relaxation time (IVRT), and pulmonary venous Ar duration had significant relations with mean pulmonary capillary wedge pressure (PCWP). The ratio of IVRT to T(E-Ea) (for MR, r=-0.92; for MS, r=-0.88; both P<0.001) and the ratio of IVRT to tau (for MR, r=-0.74; for MS, r=-0.85; both P<0.001) had the best correlations with PCWP. In 54 repeat studies, including those performed after MV repair or replacement, these ratios tracked well the changes in PCWP and readily identified changes in mean PCWP by > or =5 mm Hg. A similar correlation was noted in 13 patients with atrial fibrillation (r=-0.92, P<0.01) and in a prospective group of 14 patients with MR (r=-0.93, P<0.001). The ratio of IVRT to T(E-Ea) or to tau can be readily applied for estimating mean PCWP in patients with MVD and can track changes in PCWP after valve surgery.