Reduction In Pulmonary Capillary Wedge Pressure Research Articles

Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

Challenging the Hemodynamic Hypothesis in Heart Failure With Preserved Ejection Fraction: Is Exercise Capacity Limited by Elevated Pulmonary Capillary Wedge Pressure?

Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP should improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin to acutely lower PCWP during exercise in patients with HFpEF. Thirty patients with HFpEF (70±6 years of age; 63% female) underwent 2 bouts of upright, seated cycle exercise dosed with sublingual nitroglycerin or placebo control every 15 minutes in a single-blind, randomized, crossover design. PCWP (right heart catheterization), oxygen uptake (breath × breath gas exchange), and cardiac output (direct Fick) were assessed at rest, 20 Watts (W), and peak exercise during both placebo and nitroglycerin conditions. PCWP increased from 8±4 to 35±9 mm Hg from rest to peak exercise with placebo. With nitroglycerin, there was a graded decrease in PCWP compared with placebo at rest (-1±2 mm Hg), 20W (-5±5 mm Hg), and peak exercise (-7±6 mm Hg; drug × exercise stage P=0.004). Nitroglycerin did not affect oxygen uptake at rest, 20W, or peak (placebo, 1.34±0.48 versus nitroglycerin, 1.32±0.46 L/min; drug × exercise P=0.984). Compared with placebo, nitroglycerin lowered stroke volume at rest (-8±13 mL) and 20W (-7±11 mL), but not peak exercise (0±10 mL). Sublingual nitroglycerin lowered PCWP during submaximal and maximal exercise. Despite reduction in PCWP, peak oxygen uptake was not changed. These results suggest that acute reductions in PCWP are insufficient to improve exercise capacity, and further argue that high PCWP during exercise is not by itself a limiting factor for exercise performance in patients with HFpEF. URL: https://www. gov; Unique identifier: NCT04068844.

Transinnominate Impella 5.5 insertion as a bridge to transplantation in a pediatric patient in refractory cardiogenic shock.

Transinnominate Impella 5.5 insertion as a bridge to transplantation in a pediatric patient in refractory cardiogenic shock.

Early Hemodynamic Changes following Surgical Ablation of the Right Greater Splanchnic Nerve for the Treatment of Heart Failure with Preserved Ejection Fraction.

Background: Permanent ablation of the right greater splanchnic nerve (GSN) has previously been demonstrated to improve quality of life and functional outcomes, as well as reduce abnormally high intracardiac filling pressures, in patients with heart failure with preserved ejection fraction (HFpEF) at 1, 3 and 12 months following the procedure. We hypothesize that hemodynamic changes that ensue from surgical right GSN ablation would be apparent as early as 24 h after the medical intervention. Methods and Results: This is a prespecified analysis of a single-arm, two-center, open-label study evaluating the effects of right GSN ablation via thoracoscopic surgery in HFpEF patients with pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg with supine cycle ergometry. A total of seven patients (median age 67 years, 29% female) underwent GSN removal followed by invasive right heart catheterization within 24 h. GSN ablation resulted in a significant reduction in PCWP 24 h after the procedure compared to baseline for both 20 W exercise (baseline (28.0 ± 4.3 mmHg) to 24 h (19.6 ± 6.9 mmHg); p = 0.0124) and peak exercise (baseline (25.6 ± 2.4 mmHg) to 24 h (17.4 ± 5.9 mmHg); p = 0.0025). There were no significant changes in resting or leg-up hemodynamics. Conclusions: Permanent right GSN ablation leads to a reduction in intracardiac filling pressures during exercise, apparent as early as 24 h following the procedure.

Abstract 11760: Reducing Pulmonary Capillary Wedge Pressure During Exercise Does Not Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Background: Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP would improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin (NTG) to acutely lower PCWP during exercise in patients with HFpEF. Methods: In a preliminary analysis of a clinical trial, 15 patients with HFpEF (69±6 years, 60% female) underwent 2 upright, seated cycle exercise tests dosed with sublingual NTG or placebo control (CON), every 15 minutes in a single-blind, cross-over design. A right heart catheter was used to measure end-expiratory PCWP and cardiac output (Qc, direct Fick). Oxygen uptake was measured using breath-by-breath system. Measures were made at rest, 20W, and peak exercise. Results: PCWP increased from 6.0±2.4 to 33.7±7.4 mmHg from rest to peak exercise with placebo. With NTG, PCWP increased significantly less from 4.5±3.1 to 26.3±5.9 mmHg (drug x exercise p = 0.019). There was no change in peak VO 2 with NTG (CON: 1.25±0.36 vs NTG: 1.26±0.41 L/min, drug x exercise p = 0.986, Figure ). Peak Qc was similar between conditions (Qc: CON 10.4±2.3 vs 10.8±3.2 L/min). During submaximal exercise, PCWP was lower with NTG with no difference in VO 2 (PCWP: CON 21.2±6.5 vs NTG 16.6±6.4 mm Hg, VO 2 CON:0.87±0.17 vs NTG 0.86±0.17 L/min) but with a lower stroke volume (NTG: 90±18 vs CON: 98±21 ml). Conclusions: Sublingual nitroglycerin effectively lowered PCWP during submaximal and maximal exercise. Despite this reduction in PCWP, peak VO 2 was not changed. These results suggest acutely lowering PCWP is insufficient to improve exercise capacity and raises the possibility that high PCWP during exercise is a secondary phenomenon rather than a primary cause of exercise intolerance in patients with HFpEF.

Feasibility and efficacy of transcatheter interatrial shunt devices for chronic heart failure: a systematic review and meta‐analysis

To assess the feasibility and efficacy of interatrial shunt devices (IASD) for the treatment of chronic heart failure (CHF). MEDLINE and the Cochrane Central Register of Controlled Trials from inception until April 2021 were searched for prospective studies investigating dedicated transcatheter IASD for the treatment of CHF. Standardised mean differences were calculated for the within-group changes before and after implantation of the IASD. The pre-defined primary outcome was change in 6-min walking distance (6MWD) from baseline to 12 months. Other outcomes were change in New York Heart Association class, health-related quality of life (HRQoL), echocardiographic and haemodynamic data, device performance and safety. Subgroup analyses were crude univariable meta-regression analyses. Six studies (five single-arm open-label studies, one sham-controlled trial) were included. In these, 226 patients underwent IASD implantation using four different devices. From baseline to 12 months, 6MWD increased by 28.1m [95% confidence interval (CI) 10.9-45.3] with no evidence for a difference between devices (P for interaction=0.66) and patients with left ventricular ejection fraction (LVEF) >40% or ≤40% (P for interaction=0.21). At 12 months, HRQoL improved by 17.7 points (95% CI 10.8-24.6) and pulmonary capillary wedge pressure (PCWP) decreased by 2.0 mmHg (95% CI -3.6 to -0.4). There were no changes in LVEF or N-terminal pro brain natriuretic peptide during follow-up. Shunt patency ranged from 50% for the first-generation v-Wave to 100% for the Corvia IASD II and the second-generation v-Wave system, respectively. The summary risk of serious adverse device-related effects was 8% (95% CI 1-20) at 12 months. Interatrial shunt device implantation in CHF is feasible and associates with improved submaximal exercise capacity (measured by 6MWD) and HRQoL, and reductions in PCWP.

Longitudinal BNP follow-up as a marker of treatment response in acute heart failure: Relationship with objective markers of decongestion

IntroductionResults of studies that examined the value of B-type natriuretic peptide (BNP) reduction as a marker of decongestion have been inconsistent. We investigated whether longitudinal admission-to-discharge BNP reduction can be used to monitor decongestion during acute heart failure (HF). MethodsWe used the ESCAPE trial data to study the relationship between the magnitude of BNP reduction and various clinical and objective markers of decongestion. ResultsAdmission-to-discharge reduction in BNP was recorded in 245 patients who were divided into tertiles (tertile 1 had BNP reduction<27pg/mL, tertile 2 had BNP reduction 27–334pg/mL and tertile 3 had BNP reduction>334pg/mL). There were significant differences across tertiles with regard to resolution of jugular venous distension (JVD, P=0.014) and orthopnea (P=0.04) on discharge, admission-to-discharge weight loss (P=0.002), and admission-to-discharge reduction in inferior vena cava (IVC) diameter (P=0.0001). Compared with the first tertile, patients in the third tertile had significantly higher frequency of resolution of JVD (univariate OR 2.657, P=0.004) and orthopnea (univariate OR 2.083, P=0.032) on discharge, more weight loss (P=0.001), higher IVC diameter reduction (P<0.0001), and higher reduction in pulmonary capillary wedge pressure (PCWP) from admission to day of PAC removal compared with first tertile (P<0.0001). Using the whole cohort, we found a significant correlation between admission-to-discharge BNP reduction and admission-to-discharge weight loss (n=232, r=0.211, P=0.001), admission-to-discharge reduction in IVC diameter (n=99, r=0.360, P<0.0001) and reduction in PCWP from admission to the day of pulmonary artery catheter removal (n=92, r=0.242, P=0.02). ConclusionAdmission-to-discharge BNP reduction is a reasonable marker of treatment response in HF that correlated with clinical and objective markers of decongestion.

Rationale and Design of the Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (Reduce LAP-HF) Trial

ObjectiveHeart failure with preserved ejection fraction (HFpEF) is characterized by elevated left atrial pressure during rest and/or exercise. The Reduce LAP-HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial will evaluate the safety and performance of the Interatrial Shunt Device (IASD) System II, designed to directly reduce elevated left atrial pressure, in patients with HFpEF. MethodsThe Reduce LAP-HF Trial is a prospective, nonrandomized, open-label trial to evaluate a novel device that creates a small permanent shunt at the level of the atria. A minimum of 60 patients with ejection fraction ≥40% and New York Heart Association functional class III or IV heart failure with a pulmonary capillary wedge pressure (PCWP) ≥15 mm Hg at rest or ≥25 mm Hg during supine bike exercise will be implanted with an IASD System II, and followed for 6 months to assess the primary and secondary end points. Safety and standard clinical follow-up will continue through 3 years after implantation. Primary outcome measures for safety are periprocedural and 6-month major adverse cardiac and cerebrovascular events (MACCE) and systemic embolic events (excluding pulmonary thromboembolism). MACCE include death, stroke, myocardial infarction, or requirement of implant removal. Primary outcome measures for device performance include success of device implantation, reduction of PCWP at rest and during exercise, and demonstration of left-to-right flow through the device. Key secondary end points include exercise tolerance, quality of life, and the incidence of heart failure hospitalization. ConclusionReduce LAP-HF is the first trial intended to lower left atrial pressure in HFpEF by means of creating a permanent shunt through the atrial septum with the use of a device. Although the trial is primarily designed to study safety and device performance, we also test the pathophysiologic hypothesis that reduction of left atrial pressure will improve symptoms and quality of life in patients with HFpEF.

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.

Clinical benefits of partial circulatory support in New York Heart Association Class IIIB and Early Class IV patients

Full mechanical support with a left-ventricular assist device (LVAD) is generally limited to end-stage heart-failure patients. We have been studying the safety and efficacy of the partial support Synergy® Pocket Micro-pump as bridge-to-transplant in a less-sick group of patients as a prelude to a study of its use for destination therapy. The CircuLite® Synergy device is implanted via a small right-sided thoracotomy with an inflow cannula in the left atrium and an outflow graft connected to the right subclavian artery without the use of extracorporeal circulation. The micro-pump is the size of an AA battery, sits in the 'pacemaker' pocket subcutaneously in the right clavicular groove and pumps up to 3.0 l min⁻¹ from the left atrium to the right subclavian artery. The device has been implanted in 27 patients awaiting cardiac transplant (22 males), age 54.8 ± 10.0 years with ejection fraction (EF) 21 ± 6%, mean arterial pressure 73.5 ± 8.8 mm Hg, pulmonary capillary wedge pressure (PCWP) 27.5 ± 7.8 mm Hg and cardiac index (CI) 2.0 ± 0.4 l min⁻¹ m⁻². Duration of support has ranged from 6 to 281 days. Right-heart catheterization showed significant hemodynamic improvement in the short- and intermediate term after implant, with increases in CI from 2.0 ± 0.4 to 2.8 ± 0.6 l min⁻¹ m⁻² (p < 0.001) and reductions in PCWP from 28 ± 6 to 18 ± 7 mm Hg (p = 0.002) at an average of 9.5 ± 5.5 weeks. The Synergy device provides partial hemodynamic support and its use is associated with significantly improved hemodynamics, thus appearing to interrupt and partially reverse the progressive hemodynamic deterioration typical of end-stage heart failure. Ongoing efforts are aimed at demonstrating additional clinical benefits and continuing to further improve the risk/benefit ratio.

NON-INVASIVE DETECTION OF PCWP IN DECOMPENSATED HEART FAILURE PATIENTS TREATED WITH INTRAVENOUS HIGH-DOSE FUROSEMIDE AND SMALL-VOLUME HYPERTONIC SALINE SOLUTION: RELATIONSHIP WITH BNP AND BIOIMPEDANCE

Background: Decompansated heart failure (DHF) is a broad of spectrum of signs and symptoms characterized by fluid’s accumulation in the interstitial space of the lungs and whole body. We evaluate the non-invasive detection of pulmonary capillary wedge pressure (PCWP) by Tissue Doppler Analysis DHF patients underwent treatment with intravenous high-dose furosemide and small-volume hypertonic saline solution (HSS). Moreover we investigate its relationship with changes of BNP plasma levels and Whole-body (WB) and segmental (Seg) bioelectrical impedance analysis (BIA), a non-invasive tool useful to estimate the hydration status and fluid distribution. Methods and Results: 66 consecutive patients (63 to 82 yr, 43 men) admitted for DHF (EF<45%, NYHA class III-IV) underwent tailored therapy with intravenous furosemide and HSS were enrolled. 22 patients with compensated left ventricular dysfunction and 22 healthy subjects were considered as controls. WB and Seg BIA parameters were drawn at hospital entry and after clinical stabilization with treatment. At discharge there was a significant reduction of PCWP (-7 mmHg, p<.001) as BNP levels (p<.001) and significant increase of BIA parameters (p<.001) in DHF patients. Furthermore significant correlations of PCWP with BNP serum levels (p<.001) and BIA parameters (p<.001) and of BNP levels and BIA parameters (p<.001) at baseline and at clinical stabilization correlation were found. Conclusion: our data suggest that non-invasive evaluation of PCWP is a valuable and useful way in management of DHF. Moreover it is related to neuro-hormonal activation and whole-body and pulmonary fluid accumulation in these patients. High-dose of intravenous furosemide plus HSS are well tolerated and improve the in-hospital outcome with an effective hemodynamic stabilization, the normalization of hydration status and a positive neuro-hormonal modulation.

Effects of heat and cold stress on central vascular pressure relationships during orthostasis in humans

Central venous pressure (CVP) provides information regarding right ventricular filling pressure, but is often assumed to reflect left ventricular filling pressure. It remains unknown whether this assumption is correct during thermal challenges when CVP is elevated during skin-surface cooling or reduced during whole-body heating. The primary objective of this study was to test the hypothesis that changes in CVP reflect those in left ventricular filling pressure, as expressed by pulmonary capillary wedge pressure (PCWP), during lower-body negative pressure (LBNP) while subjects are normothermic, during skin-surface cooling, and during whole-body heating. In 11 subjects, skin-surface cooling was imposed by perfusing 16 degrees C water through a water-perfused suit worn by each subject, while heat stress was imposed by perfusing 47 degrees C water through the suit sufficient to increase internal temperature 0.95 +/- 0.07 degrees C (mean +/- s.e.m.). While normothermic, CVP was 6.3 +/- 0.2 mmHg and PCWP was 9.5 +/- 0.3 mmHg. These pressures increased during skin-surface cooling (7.8 +/- 0.2 and 11.1 +/- 0.3 mmHg, respectively; P < 0.05) and decreased during whole-body heating (3.6 +/- 0.1 and 6.5 +/- 0.2 mmHg, respectively; P < 0.05). The decrease in CVP with LBNP was correlated with the reduction in PCWP during normothermia (r = 0.93), skin-surface cooling (r = 0.91), and whole-body heating (r = 0.81; all P < 0.001). When these three thermal conditions were combined, the overall r value between CVP and PCWP was 0.92. These data suggest that in the assessed thermal conditions, CVP appropriately tracks left ventricular filling pressure as indexed by PCWP. The correlation between these values provides confidence for the use of CVP in studies assessing ventricular preload during thermal and combined thermal and orthostatic perturbations.

The effect of altering haemodynamics on the plasma concentrations of natriuretic peptides in heart failure

Natriuretic peptide levels reflect haemodynamics in patients with heart failure and may serve as biochemical markers of cardiac filling pressures. The purpose of this study was to detect differences in the kinetic profile between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent vasodilatation. Sixteen men and four women aged 63.0+/-10.4 (mean+/-S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary capillary wedge pressure (PCWP)>18 mm Hg, received a 24-h infusion of nitroglycerin (N=8) or nicorandil (N=12). A reduction of PCWP was achieved for the duration of the study. Natriuretic peptides were measured by radioimmunoassay at baseline, 1, 3, 6, 12 and 24 h. PCWP and right atrial pressure fell rapidly and then increased modestly. ANP and N-ANP demonstrated a similar pattern. In contrast, BNP and N-BNP levels fell steadily throughout the observation period. This was accompanied by a continuous reduction of systemic vascular resistance (SVR). PCWP was highly correlated to the levels of all the natriuretic peptides. Using a longitudinal regression model evaluating responses over time, we found separate, significant relationships between all peptides and haemodynamic variables The atrial natriuretic peptides reflect rapid changes in filling pressures while the B-type peptides respond much slower. B-type peptides are less sensitive to short-term changes in filling pressures, but should reflect changes in SVR better during vasodilator therapy.

Short‐term effects of levosimendan and prostaglandin E1 on hemodynamic parameters and B‐type natriuretic peptide levels in patients with decompensated chronic heart failure

Both levosimendan and prostaglandin E1 (PGE1) have beneficial effects on hemodynamic parameters and outcome compared to dobutamine in decompensated chronic heart failure (CHF). We compared short-term effects of levosimendan versus PGE1 on hemodynamic parameters and B-type natriuretic peptide levels (BNP) in patients with decompensated CHF. 73 patients (cardiac index < 2.5 L/min/m2, pulmonary capillary wedge pressure (PCP) >15 mmHg) with decompensated CHF were randomised to treatment with either a 24 h-infusion of levosimendan (n=38) or a chronic infusion of PGE1 (n = 35). Hemodynamic parameters and BNP were measured at baseline, 24 and 48 h, BNP levels were also measured after 1 week. Baseline characteristics including concomitant medication were similar in both groups. Levosimendan and PGE1 increased cardiac output (CO) after 24 and 48 h. Levosimendan increased CO twice as much as PGE1 (24 h: Levosimendan +1.1 +/- 0.1 L/min, PGE1 +0.6 +/- 0.1 L/min, p < 0.001). Both drugs produced a comparable reduction in PCP and pulmonary artery pressure after 24 and 48 h. Levosimendan decreased BNP by 28% after 24 h and 22% after 48 h, but effects disappeared after 1 week. In contrast, PGE1 decreased BNP by 15% after 48 h (no change at 24 h), but a decrease of 20% was sustained at 1 week. The differential beneficial effects of levosimendan (greater increase in CO) and PGE1 (sustained decrease in BNP) may have a potential impact on clinical outcome.

Intravenous Nesiritide vs Nitroglycerin for Treatment of Decompensated Congestive Heart Failure

Decompensated congestive heart failure (CHF) is the leading hospital discharge diagnosis in patients older than 65 years. To compare the efficacy and safety of intravenous nesiritide, intravenous nitroglycerin, and placebo. Randomized, double-blind trial of 489 inpatients with dyspnea at rest from decompensated CHF, including 246 who received pulmonary artery catheterization, that was conducted at 55 community and academic hospitals between October 1999 and July 2000. Intravenous nesiritide (n = 204), intravenous nitroglycerin (n = 143), or placebo (n = 142) added to standard medications for 3 hours, followed by nesiritide (n = 278) or nitroglycerin (n = 216) added to standard medication for 24 hours. Change in pulmonary capillary wedge pressure (PCWP) among catheterized patients and patient self-evaluation of dyspnea at 3 hours after initiation of study drug among all patients. Secondary outcomes included comparisons of hemodynamic and clinical effects between nesiritide and nitroglycerin at 24 hours. At 3 hours, the mean (SD) decrease in PCWP from baseline was -5.8 (6.5) mm Hg for nesiritide (vs placebo, P<.001; vs nitroglycerin, P =.03), -3.8 (5.3) mm Hg for nitroglycerin (vs placebo, P =.09), and -2 (4.2) mm Hg for placebo. At 3 hours, nesiritide resulted in improvement in dyspnea compared with placebo (P =.03), but there was no significant difference in dyspnea or global clinical status with nesiritide compared with nitroglycerin. At 24 hours, the reduction in PCWP was greater in the nesiritide group (-8.2 mm Hg) than the nitroglycerin group (-6.3 mm Hg), but patients reported no significant differences in dyspnea and only modest improvement in global clinical status. When added to standard care in patients hospitalized with acutely decompensated CHF, nesiritide improves hemodynamic function and some self-reported symptoms more effectively than intravenous nitroglycerin or placebo.

Hemodynamics as surrogate end points for survival in advanced heart failure: An analysis from FIRST

Background Hemodynamics often are used as surrogate end points in phase II trials of acute heart failure (HF). We reviewed the Flolan International Randomized Survival Trial (FIRST) database to identify the hemodynamic variables that best predict survival in patients with advanced HF receiving epoprostenol therapy and to determine whether hemodynamics could predict the overall effect of a drug. Methods The trial enrolled 471 patients with class IIIb/IV HF and ejection fraction ≤25% for ≥3 months, all of whom underwent screening pulmonary artery catheter insertion. Patients were randomly assigned to receive either epoprostenol (n = 201) or placebo (n = 235); epoprostenol therapy was guided by pulmonary artery catheter measures, and standard treatment was guided by clinical findings. Multivariable modeling was used to identify and quantify the demographic, clinical, and hemodynamic variables most associated with 1-year survival. Results In multivariable modeling, HF class, decreased pulmonary capillary wedge pressure (PCWP), and age best predicted 1-year survival. After adjustment for age and HF class, decreased PCWP still significantly predicted survival (hazard ratio, 0.96 for every 1–mm Hg decrease; 95% confidence interval, 0.94 to 0.99; P = .003). Survival was significantly higher with decreases in PCWP ≥9 versus <9 mm Hg, even after adjustment for age and HF class. Survival of patients in the PCWP ≥9 group was comparable with, and that of the PCWP <9 group was significantly higher than, survival of patients in the control group (hazard ratio, 1.44; 95% confidence interval, 1.05 to 1.99; P = .024). Conclusions The reduction in PCWP was the hemodynamic measure most predictive of survival in patients with advanced HF. However, patients with a ≥9–mm Hg decrease had no better survival than patients in the control group, who had limited changes in hemodynamics. Thus, improvement in hemodynamics may not predict the overall effect of a drug. (Am Heart J 2001;141:908-14.)

Time Course and Extent of Improvement of Dysfunctioning Myocardium in Patients with Coronary Artery Disease and Severely Depressed Left Ventricular Function after Revascularization: Correlation with Positron Emission Tomographic Findings

Time Course and Extent of Improvement of Dysfunctioning Myocardium in Patients with Coronary Artery Disease and Severely Depressed Left Ventricular Function after Revascularization: Correlation with Positron Emission Tomographic Findings

Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure

OBJECTIVESWe sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin.BACKGROUNDLevosimendan is a calcium sensitizer for treatment of acute decompensated heart failure.METHODSA double-blind, placebo-controlled, randomized, multicenter, parallel-group study included 151 adult patients. Levosimendan was given as a 10-min intravenous bolus of 3, 6, 12, 24 or 36 μg/kg, followed by a 24-h infusion of 0.05, 0.1, 0.2, 0.4 or 0.6 μg/kg/min, respectively. Dobutamine, for comparative purposes, was given as an open-label infusion (6 μg/kg/min). The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following: 1) a ≥15% increase in stroke volume (SV) at 23 h to 24 h; 2) a ≥25% decrease in pulmonary capillary wedge pressure (PCWP) (and ≥4 mm Hg) at 23 h to 24 h; 3) a ≥40% increase in cardiac output (CO) (with change in heart rate [HR] <20%); 4) a ≥50% decrease in PCWP during two consecutive measurements.RESULTSThe response rate to levosimendan ranged from 50% at the lowest dose to 88% at the highest dose (compared with placebo 14%, dobutamine 70%). A dose-response relationship was demonstrated for levosimendan on increases in CO and SV, and reductions in PCWP during the infusion (for all, p ≤ 0.001). Headache (9%), nausea (5%) and hypotension (5%) were the most frequently reported adverse events at higher dosages.CONCLUSIONSDosing of levosimendan with a 10-min bolus of 6 to 24 μg/kg followed by an infusion of 0.05 to 0.2 μg/kg/min is well tolerated and leads to favorable hemodynamic effects.

Comparison of hemodynamic effects and plasma cyclic guanosine monophosphate of nicorandil and nitroglycerin in patients with congestive heart failure

Hemodynamic tolerance has been observed within several hours of continuous infusion of nitroglycerin (NTG). We examined the hemodynamic parameters as well as femoral arterial and venous cyclic guanosine monophosphate (cGMP) concentrations during intravenous infusion of NTG or nicorandil, a nitrate and potassium channel opener, in patients with congestive heart failure. Doses of NTG or nicorandil were titrated to achieve a ≥25% reduction in pulmonary capillary wedge pressure (PCWP) within 1 hour, and the infusion was maintained at a constant rate for 24 hours. The reduction in PCWP and mean arterial blood pressure was identical after a 1-hour infusion of either NTG or nicorandil. In the NTG group, PCWP and mean blood pressure were not significantly different from the baseline value at 12 hours, but in the nicorandil group PCWP and mean blood pressure remained significantly lower than the preinfusion value for 24 hours. The cGMP production with NTG (assessed by the difference between the plasma arterial and venous cGMP level) paralleled the changes in PCWP, suggesting that the plasma arteriovenous cGMP difference is a biochemical indicator of nitrate tolerance. Although the sustained decrease in PCWP was observed in the nicorandil group, cGMP production with nicorandil was also attenuated at 24 hours of continuous infusion. These findings suggest that the absence of the hemodynamic tolerance of nicorandil, a nitrate and potassium channel opener, is likely due to its action as a potassium channel opener, and not to its nitrate activity.

Effects of dobutamine and/or nitroprusside on the pulmonary circulation in patients with pulmonary hypertension secondary to end-stage heart failure

Nine NYHA class III-IV patients awaiting heart transplantation (HTx) were studied with a right ventricular ejection fraction (RVEF) catheter. The first aim of the study was to explore the pulmonary and systemic circulatory effects of dobutamine (D) and/or nitroprusside (N) in these patients. The second aim was to search for the parameter(s) among those usually measured that best predicted RVEF. Baseline data were recorded after 30 minutes of stabilization. Then, three drug regimens were administered in a randomized order for 30 minutes each: D, 4 μg/kg/min; N, 0.25 to 1.0 μg/kg/min; and their combination. Significant changes in RV loading and function were observed with all three therapies. The combination of both drugs was superior to either drug alone. The best predictor of RVEF was pulmonary arterial elastance. The second best was pulmonary capillary wedge pressure (PCWP). Pulmonary artery pressures, pulmonary vascular resistances, and transpulmonary gradient (TPG) were of less predictive value, as shown by a multiple regression analysis. None of the drugs showed any selectivity for the pulmonary vasculature, because the ratio PVRI/SVRI was never changed significantly. Selective pulmonary arterial vascular smooth muscle relaxation is probably not the most important mechanism to explain the unloading and improvement in function of the RV with D and/or N. Improved myocardial pump function appears to be the major factor in unloading the RV via reduction of PCWP and mean pulmonary artery pressure with essentially no change in TPG. The RVEF catheter provides valuable additional information in the screening of HTx candidates for pulmonary hypertension.