Elevated Pulmonary Capillary Wedge Pressure Research Articles

Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

Nitroprusside Combined with Leg Raise at the Time of Right Heart Catheterization to Differentiate Precapillary from Other Hemodynamic Forms of Pulmonary Hypertension: A Single-Center Pilot Study.

Pulmonary hypertension (PH) can arise from several distinct disease processes, with a percentage presenting with combined pre- and postcapillary pulmonary hypertension (cpcPH). Patients with cpcPH are unsuitable candidates for PH-directed therapies due to elevated pulmonary capillary wedge pressures (PCWPs); however, the PCWP is dynamic and is affected by both preload and afterload. Many patients that are diagnosed with cpcPH are hypertensive at the time of right heart catheterization which has the potential to increase the PCWP and, therefore, mimic a more postcapillary-predominant phenotype. In this small pilot study, we examine the effect of nitroprusside combined with dynamic preload augmentation with a passive leg raise maneuver in hypertensive cpcPH patients at the time of right heart catheterization to identify a more precapillary-dominant PH phenotype. Patients that met the criteria of PCWP ≤ 15 mmHg with nitroprusside infusion and PCWP ≤ 18 mmHg with nitroprusside infusion and simultaneous leg raise were started on pulmonary vascular-targeted therapy. Long-term PH therapy was well tolerated, with increased six-minute walk distance, improved WHO functional class, decreased NT-proBNP, and improved REVEAL 2.0 Lite Risk Score in this precapillary-dominant PH phenotype. This small study highlights the importance of characterizing patient physiology beyond resting conditions at the time of right heart catheterization.

Noninvasive Prediction of Pulmonary Capillary Wedge Pressure in Patients With Normal Left Ventricular Ejection Fraction: Comparison of Cardiac Magnetic Resonance With Comprehensive Echocardiography

Cardiac magnetic resonance (CMR) was recently reported to predict mean pulmonary capillary wedge pressure (PCWP). However, there is a paucity of data on its accuracy for estimation of PCWP in patients with normal left ventricular (LV) ejection fraction (EF). We sought to examine its accuracy against the invasive gold standard and to compare it with the accuracy of comprehensive echocardiography. Stable patients with EF of ≥50% who underwent right heart catheterization, CMR, and echocardiographic imaging within 1week were included. Pulmonary capillary wedge pressure was estimated by CMR using a previously validated equation where PCWP is estimated based on the left atrial maximum volume and LV mass. Echocardiographic estimation of PCWP was based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines, taking into account the presence of myocardial disease. The mean age of the 79 patients was 55±15years, and 58.2% were female. There were 33 patients with PCWP >15mm Hg by right heart catheterization. Cardiac magnetic resonance prediction of PCWP had an area under the curve (AUC)=0.72. In comparison, echocardiographic prediction of PCWP showed a higher accuracy (AUC=0.87 vs AUC=0.72; P=.008). In patients with normal LV EF, CMR estimation of mean PCWP based on LV mass and left atrial volume has modest accuracy for detecting patients with mean PCWP >15mm Hg. Comprehensive echocardiography predicts elevated PCWP with higher accuracy in comparison with CMR.

Mitral E-wave to stroke volume ratio displays stronger diagnostic performance to identify elevated left ventricular filling pressures than mitral E/e' during passive leg lift: A cross-sectional study employing simultaneous echocardiography and catheterization.

Elevated filling pressure is a hallmark of heart failure (HF) and portends poor prognosis. Accurate diagnosis is challenging, given that patients with normal filling pressure at rest develop disproportionate elevation with sudden preload increase. We aimed to test the accuracy of the ratio between mitral inflow velocity (E) and left ventricular stroke volume (SV) to identify patients with elevated filling pressure with passive leg lifting (PLL) and compare this with other echocardiographic surrogates of filling pressure. Doppler echocardiography and right heart catheterization (RHC) were simultaneously performed in 37 patients (11 males, mean age 67±12 years) with exertional dyspnea. Twenty-six healthy controls (14 males, mean age 60±12 years) were added as reference. SV, cardiac output (CO), tricuspid regurgitation peak gradient (TRG), mitral E-wave (E)and early myocardial velocity (e') were obtained at rest and with PLL. E/SV, E/CO and E/e' were calculated and correlated with invasive pulmonary capillary wedge pressures (PCWP) with PLL. During PLL, E/SV (AUC=0.94) displayed stronger diagnostic ability to identify PCWP>15mmHg than E/e' (AUC=0.81), mitral E/A ratio (0.76) and resting invasive PCWP (0.84). An E/SV cutoff of>1.0 showed 88% sensitivity and 75% specificity to identify elevated PCWP. Further, 10 patients (27%) were reassigned during PLL from normal to postcapillary pulmonary hypertension (postCPH), and 6 patients (16%) switched diagnosis from precapillary PH (preCPH) to postCPH. The novel E/SV ratio identifies patients with elevated PCWP with PLL and displays stronger diagnostic performance than routinely utilized echocardiographic measures such as E/e' in addition to resting, catheterization derived PCWP.

Obesity in heart failure with preserved ejection fraction: Insights from the REDUCE LAP-HF II trial.

Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2 . As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e' were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.

Abstract 17362: Left Atrial Stiffness is Increased in Pediatric Hypertrophic Cardiomyopathy and May Be of Incremental Value in Predicting Major Adverse Cardiac Events in This Group

Background: Determining risk factors by echocardiography to prevent major adverse cardiac events (MACE) is crucial in pediatric patients with hypertrophic cardiomyopathy (HCM). Recent studies have shown that LA stiffness and strain may serve as surrogate markers in children, to differentiate elevated pulmonary capillary wedge pressure from normal and predict COVID-19 related myocardial injury. Hypothesis: LA stiffness may predict MACE in pediatric patients with HCM. Methods: We retrospectively enrolled 201 pediatric patients with HCM diagnosed by echocardiography. They were divided into two groups: MACE (n=61) and non-MACE (n=140) groups. LV systolic function, and LA strain were evaluated by conventional 2D and speckle tracking echocardiography. Noninvasive LA stiffness was calculated as the ratio of E/e’ to LA strain as depicted in the following equation: LA Stiffness= E/e ' ratio / LA Peak Strain (% -1 ). The primary outcome was a composite endpoint of MACE (including ICD placement, myomectomy, heart transplant or death) during follow-up. Results: The MACE group showed significantly decreased LV global longitudinal strain (GLS) compared to non-MACE group (GLS - 16.76 ± 5.05% vs. - 20.25 ± 3.40%, p < 0.001), even though LV ejection fraction showed no significant difference between the two groups. LA peak strain was significantly reduced (21.96 ± 7.24% vs. 30.80 ± 7.10%, p < 0.001), whereas, noninvasive LA stiffness was significantly increased (0.72 ± 0.48 % -1 vs. 0.34 ± 0.16 % -1 , p < 0.001) in the MACE group. Among the LV diastolic indices, LA stiffness was the superior-most index for predicting MACE (see Table 1, Figure 1) (AUC: 0.814, cut off value: 0.49% -1 ). Also, LA stiffness was independently associated with increased risk of the composite endpoint of MACE (HR: 3.26 [95% CI: 1.77 -5.99]; P < 0.001, see Table 2). Conclusion: LA stiffness is a newly described index in children, that may be of incremental value in predicting risk of MACE in pediatric HCM patients.

Abstract 14855: Noninvasive Prediction of Pulmonary Capillary Wedge Pressure in Patients With Normal LV EF: Comparison of CMR With Echocardiography

Background: Cardiac magnetic resonance (CMR) was recently reported to predict mean pulmonary capillary wedge pressure (PCWP) with the best accuracy in mid-rage or reduced left ventricular (LV) ejection fraction (EF). . There is a paucity of data on the accuracy of CMR estimation of PCWP in patients with normal left ventricular (LV) ejection fraction (EF) or on how CMR compares with echocardiography in these patients. Methods: Stable patients with EF of ≥50%, who underwent right heart catheterization (RHC), CMR, and echocardiographic imaging within one week were included. PCWP was estimated by CMR using a previously validated equation where PCWP is estimated based on the left atrial maximum volume (LAV) and left ventricular mass (LVM) as PCWP=6.1352+ (0.07204*LAV) + (0.02256*LVM). Echocardiographic estimation of PCWP was based on 2016 ASE/EACVI guidelines taking into account the presence of myocardial disease and pulmonary vein atrial velocity. Results: Mean age was (54.6 ± 15.2), 58.2% females. There were 33 patients with PCWP > 15 mmHg by RHC and 46 with a normal PCWP by right heart catheterization. The table shows sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the two imaging modalities. CMR prediction of PCWP had an AUC=0.72. In comparison, echocardiographic prediction of PCWP had significantly higher accuracy (AUC=0.87 vs. AUC=0.72; P- value=0.008). Conclusion: In patients with normal LV EF, CMR estimation of mean PCWP has an acceptable accuracy for detecting patients with mean PCWP>15 mmHg. Echocardiography predicts elevated PCWP with a significantly higher sensitivity, specificity, and overall accuracy in comparison with CMR.

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

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

Using Cardiac MRI to Identify Elevated Pulmonary Capillary Wedge Pressures in Patients With Obesity

Using Cardiac MRI to Identify Elevated Pulmonary Capillary Wedge Pressures in Patients With Obesity

Acute Pulmonary Edema and NSTEMI.

Emergency medicine residents and medical students on emergency medicine rotation. Acute pulmonary edema is a common and potentially fatal presentation in the emergency department. More than 1 million patients are admitted annually with a diagnosis of pulmonary edema secondary to cardiac causes.1 Pulmonary edema is broadly split into two main categories: cardiogenic and noncardiogenic. Cardiogenic pulmonary edema is characterized by acute dyspnea caused by the accumulation of fluid within the lung's interstitial and/or alveolar spaces, which is the result of acutely elevated cardiac filling pressures.2 Noncardiogenic pulmonary edema is characterized by fluid accumulation within the alveolar space in the absence of elevated pulmonary capillary wedge pressure.2 These patients often present critically ill, and rapid identification and aggressive management is paramount in caring for patients with pulmonary edema. Dyspnea is the most common presentation with a sensitivity of 89% but a low specificity of 51%.3 Workup of pulmonary edema often includes laboratory testing, electrocardiogram (EKG), chest x-ray (CXR), and often bedside ultrasound (US) and echocardiography.4 Pulmonary edema management depends on the etiology but is often focused on preload and afterload reduction. Diuretics, nitrates, and optimizing ventilatory support through non-invasive and invasive strategies are the mainstay of treatment. At the end of this practice oral boards case, the learner will:1) recognize unstable vital signs (VS) and intervene to stabilize ventilation and oxygenation, 2) demonstrate the ability to obtain a complete medical history including the important characteristics of chest pain, 3) demonstrate an appropriate exam on a patient, 4) order the appropriate evaluation studies for a patient with complaints of dyspnea, 5) interpret the results of diagnostic evaluation and diagnose Non- ST elevation myocardial infarction (NSTEMI) and pulmonary edema, 6) order appropriate management of pulmonary edema and NSTEMI, and 6) demonstrate effective communication with patient and family members. Practice oral boards. Immediate Feedback was solicited from the learners and observers participating in the case both by verbal discussion and completion of a rating for the case following the debriefing. The efficacy of the educational content was assessed by comparing scoring measures across residents based on the training year. Scoring measures of the American College of Graduate Medical Education (ACGME) core competencies were performed using a scale from 1 - 8, 1-4 being unacceptable performance and 5 - 8 being acceptable. Efficacy was assumed based on full completion of the case by the residents who acted as practice oral board candidates, and a debriefing session followed to discuss the key components of the case. This case was presented to twelve Emergency Medicine Residents, seven PGY 1 and five PGY 2 at a relatively new residency program. The overall average score for the residents was 5.62. The PGY 1 Residents' average on the case was 5.56, and the average for the PGY 2 Residents was slightly better at 5.70. The slight improvement noted by the PGY 2 Residents is likely attributable to more clinical experience; however, both classes did not have any prior exposure to the oral board format until this simulated experience. Six residents completed all critical actions in the case. Of those who missed a critical action, failing to diagnose NSTEMI and consulting cardiology were the most common. All learners found educational value in the case with an overall rating of 4.83 (1-5 Likert scale, 5 being excellent). Acute pulmonary edema and NSTEMI are common diagnoses that will be frequently encountered for most emergency physicians. This case highlights the need for early identification and aggressive management of the patient presenting with respiratory distress. The differential for respiratory distress is large, but most learners were able to quickly identify pulmonary edema based on the exam findings of jugular vein distention (JVD), rales, and lower extremity edema. Most learners quickly escalated to a non-rebreather mask and ultimately to BPAP (bilevel positive airway pressure) without requesting to intubate the patient. There was notable variation in the approach to administering nitrates, but most ordered an intravenous (IV) nitroglycerin (NTG) drip and requested pharmacy assistance in dosing. Diuretics were ordered by all the learners, but some were hesitant to start early because they felt the effect would be delayed. Some of the residents did not identify ischemic changes on the EKG at first glance but did request to review a second time when the troponin result was positive. All residents gave aspirin after noting the positive troponin, but not all were able to make a clear diagnosis of NSTEMI or consult cardiology. Although the case was relatively straightforward, residents enjoyed early diagnosis and aggressive management of the patient with impending respiratory failure. Many residents are asking for an ultrasound early in the workup of this patient presenting in respiratory distress. Although not a critical action in this case, it highlights the emphasis placed on ultrasonography in the current emergency medicine curriculum. Pulmonary Edema, Cardiovascular emergencies, NSTEMI.

Can echocardiographic parameters effectively predict elevated pcwp in heart transplant patients?

Abstract Funding Acknowledgements Type of funding sources: None. PCWP measurement remains the gold standard for the diagnosis of Heart Failure with preserved ejection fraction. Nevertheless, right heart catheterization (RHC) is a last step procedure nowadays, with most of the patients diagnosed solely by transthoracic echocardiography (TTE) parameters, as it is widely available and not associated with the risks of the invasive procedures. Heart transplant (HT) patients, on the other hand, routinely perform RHC as follow-up for rejection surveillance, allowing frequent invasive hemodynamic assessment. Purpose Evaluate the association between TTE parameters and the invasively measured pulmonary capillary wedge pressure (PCWP) by RHC in HT patients. Methods A retrospective analysis of consecutive HT patients submitted to RHC between February 2016 and November 2021, who previously performed TTE, was made. The area under the curve (AUC) was performed to evaluate the association between several TTE parameters (left ventricular (LV) end-diastolic diameter (LV EDD), LV end-systolic diameter (LV ESD), LV ejection fraction (LV EF), interventricular septum wall thickness (ST), LV global longitudinal strain (GLS), left atrium volume index (LAVi), transmitral E/A ratio (E/A), LV E/e’ ratio (E/e’), E velocity deceleration time (DT), isovolumetric relaxation time (IV RT), tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP)) and elevated PCWP (defined as >15mmHg). Statistical differences with a p-value <0.05 were considered significant. Results A total of 127 RHC were performed during the study period. Mean age was 50 years, 79% (n=100) were male, mean LV EF 58 ± 10% and mean BNP 808 ± 984 pg/mL. Mean PCWP was 12 ± 6 mmHg, with 28% (n=35) with a value higher than 15mmHg. AUC results of several TTE parameters for the prediction of elevated PCWP are depicted in Table 1. LV EF (AUC 0.702, p = 0.001) and GLS (AUC 0.768, p = 0.07) were significantly correlated with elevated PCWP, while the remaining parameters failed to do so. Conclusion In this HT group, several TTE indices commonly employed for non-invasive estimation of increased intraventricular pressures, including E/e', E/A ratio, LAVi, and sPAP, showed a poor correlation with elevated PCWP. GLS, a TTE parameter widely used to assess subclinical dysfunction were the parameter with the most robust association with elevated PCWP in this population, demonstrating that it has the potential to be used in routine clinical practice.

Left atrial stiffness and strain are novel indices of left ventricular diastolic function in children: validation followed by application in multisystem inflammatory syndrome in children due to COVID-19.

We hypothesized left atrial (LA) stiffness may serve as a surrogate marker in children to differentiate elevated pulmonary capillary wedge pressure (PCWP) from normal and help detect diastolic dysfunction in myocardial injury due to multisystem inflammatory syndrome in children (MIS-C). We validated LA stiffness in 76 patients (median age 10.5 years), 33 had normal PCWP (<12 mmHg) and 43 had elevated PCWP (≥12 mmHg). LA stiffness was applied to 42 MIS-C patients [28 with myocardial injury (+) and 14 without myocardial injury (-)], defined by serum biomarkers. The validation group consisted of a group with and without cardiomyopathies, whose PCWP values ranged from normal to severely elevated. Peak LA strain was measured by speckle-tracking and E/e' from apical four chamber views. Noninvasive LA stiffness was calculated as: LAStiffness=E/e'LAPeakStrain (%-1). Patients with elevated PCWP showed significantly elevated LA stiffness [median 0.71%-1 vs. 0.17%-1, P < 0.001]. Elevated PCWP group showed significantly decreased LA strain (median: 15.0% vs. 38.2%, P < 0.001). Receiver operator characteristic (ROC) curve for LA stiffness yielded an area under the curve (AUC) of 0.88 and cutoff value of 0.27%-1. In MIS-C group, ROC curve yielded an AUC of 0.79 and cutoff value of 0.29%-1 for identifying myocardial injury. In children with elevated PCWP, LA stiffness was significantly increased. When applied to children with MIS-C, LA stiffness classified myocardial injury accurately. LA stiffness and strain may serve as noninvasive markers of diastolic function in the pediatric population.

Prognostic benefit of early diagnosis with exercise stress testing in heart failure with preserved ejection fraction.

Delayed diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) can lead to poor clinical outcomes. Exercise stress testing, especially exercise stress echocardiography, plays a primary role in the early detection of HFpEF among dyspnoeic patients, but its prognostic significance is unknown, as is whether initiation of guideline-directed therapy could improve clinical outcomes in such early-stage HFpEF. Ergometry exercise stress echocardiography was performed in 368 patients with exertional dyspnoea. Heart failure with preserved ejection fraction was diagnosed by a total score of HFA-PEFF algorithm Step 2 (resting assessments) and Step 3 (exercise testing) ≥ 5 or elevated pulmonary capillary wedge pressure at rest or during exercise. The primary endpoint comprised all-cause mortality and worsening HF events. Heart failure with preserved ejection fraction was diagnosed in 182 patients, while 186 had non-cardiac dyspnoea (controls). Patients diagnosed with HFpEF had a seven-fold increased risk of composite events than that of controls [hazard ratio (HR) 7.52; 95% confidential interval (CI), 2.24-25.2; P = 0.001]. Patients with an HFA-PEFF Step 2 < 5 points but had an HFA-PEFF ≥ 5 after exercise stress testing (Steps 2-3) had a higher risk of composite events than controls. Guideline-recommended therapies were initiated in 90 patients diagnosed with HFpEF after index exercise testing. Patients with early treatment experienced lower rates of composite outcomes than those without (HR 0.33; 95% CI, 0.12-0.91; P = 0.03). Identification of HFpEF by exercise stress testing may allow risk stratification in dyspnoeic patients. Furthermore, initiation of guideline-directed therapy may be associated with improved clinical outcomes in patients with early-stage HFpEF. Delayed diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) can lead to poor clinical outcomes. Exercise stress testing, especially exercise stress echocardiography, plays a primary role in the early identification of HFpEF among dyspnoeic patients, but its prognostic significance is unknown, as is whether initiation of guideline-directed therapy could improve clinical outcomes in such early-stage HFpEF. In the current study, ergometry exercise stress echocardiography was performed in 368 patients with exertional dyspnoea. Heart failure with preserved ejection fraction was diagnosed by the established algorithm consisting of Step 2 (resting assessments) and Step 3 (exercise echocardiography or exercise right heart catheterization). The primary endpoint comprised all-cause mortality and worsening HF events. Heart failure with preserved ejection fraction was diagnosed in 182 patients and non-cardiac dyspnoea (controls) in 186 patients. Patients newly diagnosed with HFpEF had a seven-fold increased risk of composite events than that of controls. Guideline-recommended therapies were initiated in 90 patients newly diagnosed with HFpEF after index exercise testing. Patients with early treatment experienced lower rates of composite outcomes than those without. In conclusion, identification of HFpEF by exercise stress testing may allow risk stratification in patients with chronic exertional dyspnoea. Furthermore, initiation of guideline-directed therapy may be associated with improved clinical outcomes in patients with early-stage HFpEF.

Safety and Efficacy of Sildenafil for Group 2 Pulmonary Hypertension in Left Heart Failure.

Pulmonary hypertension (PH) is a multifactorial, progressive disease with poor outcomes. Group 2 PH is defined by pulmonary vascular disease with elevated pulmonary capillary wedge pressure including both left-sided obstructive lesions and diastolic heart failure (HF). Sildenafil was historically discouraged in this population as pulmonary vasodilation can lead to pulmonary edema. However, evidence suggests that sildenafil can help to treat the precapillary component of PH. This is a single center, retrospective pilot study of pediatric PH patients with left-sided HF who were treated with sildenafil for ≥ 4 weeks. HF patients without mechanical support (HF group) and HF patients with a left ventricular assist device (HF-VAD) were analyzed. The exploratory analysis described the safety and side effects of the drug. Echocardiographic parameters were compared before and after sildenafil treatment in a paired analysis. The changes in medical therapy during treatment, mechanical support, and mortality was reported; 19/22 patients tolerated sildenafil. Pulmonary edema in two patients resolved upon discontinuation of sildenafil. In the HF group, both the right atrial volume and right ventricular diastolic area decreased, and the tricuspid regurgitation (TR) S/D ratio decreased after therapy (p = 0.02). Across both the groups, four patients weaned off milrinone and seven weaned off inhaled nitric oxide. Of the thirteen HF patients, four received a transplant, and all of the nine HF-VAD patients received a transplant. Sildenafil can be safely used in carefully selected patients with HF and mixed pre/postcapillary PH with judicious titration and inpatient surveillance, with patients showing improvements in echocardiographic parameters.

Utility of E/e′ Ratio During Low-Level Exercise to Diagnose Heart Failure With Preserved Ejection Fraction

BackgroundE/e′ ratio during exercise is the key parameter in identifying elevated pulmonary capillary wedge pressure (PCWP), and thus heart failure with preserved ejection fraction (HFpEF). However, its diagnostic value is limited when mitral inflow or tissue velocities are fused during elevated heart rate. ObjectivesThe authors hypothesized that E/e‘ ratio during low-level (20 W) exercise (E/e′20W) can help diagnose HFpEF. MethodsErgometric exercise stress echocardiography was performed in 215 dyspneic patients with an EF ≥50%. The authors determined the feasibility of E/e′ ratio at each stage (frequency of patients who had measurable E/e′ without E-A fusion among 215 participants) and examined whether E/e′20W could predict normal E/e′ ratio during peak exercise (E/e′peak ≤15). The authors also evaluated whether E/e′20W could predict normal PCWP during exercise (PCWP <25 mm Hg) in a subset of participants (n = 45) who underwent exercise right heart catheterization. ResultsThe feasibility of the E/e′ ratio decreased from 100% at rest to 96.3% during 20-W exercise and 74.9% during peak exercise caused by E-A fusion. In patients with E/e′peak >15, there was an increase in E/e′ ratio from rest to 20-W exercise (11.2 ± 2.1 to 16.3 ± 3.5; P < 0.0001), but it did not change significantly from 20-W exercise to peak exercise (P = 0.12). E/e′20W predicted E/e′peak ≤15 (AUC: 0.91; P < 0.0001) with the cutoff value of ≤12.4 showing high specificity (94%) and positive predictive value (98%). During 20-W exercise, 93% of the HFpEF patients developed PCWP ≥25 mm Hg. E/e′20W predicted normal PCWP during exercise (AUC: 0.77; P = 0.01) with the cutoff value of ≤12.4 showing high specificity (83%). ConclusionsE/e′ ratio during low-level exercise is highly feasible and predicts normal E/e′ ratio or PCWP during peak exercise with high specificity. These data suggest that E/e′20W could be used as an alternative to the peak exercise value to rule out HFpEF in patients with dyspnea.

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.

Echocardiographic assessment alone is inadequate for determining elevated left sided filling pressures in patients with cardiogenic shock

Abstract Background Left atrial (LA) filling pressure assessment is of paramount importance in tailoring treatments for patients with cardiogenic shock (CS). ESC guidelines advocate for the use of mitral inflow Doppler and mitral annulus tissue Doppler measurements to predict elevated left atrial pressure in clinical practice. Echocardiographic measurement of LA pressures could reduce the need for invasive monitoring in CS patients, but its utility remains unproven in this population. Purpose We assessed the validity of mitral inflow velocity and mitral annulus velocity indices to determine LA pressures, correlating them with invasive measurement of pulmonary capillary wedge pressure (PCWP) in CS patients admitted to the cardiac intensive care unit (CICU). Methods We prospectively evaluated consecutive patients who underwent pulmonary artery catheter insertion in the CICU, measuring their haemodynamic parameters, including PCWP. This was immediately followed by a transthoracic echocardiography (TTE) performed by a critical care cardiologist, blinded to the invasive measurements. The early (E) and late (A) mitral inflow velocities were measured using mitral inflow Doppler and septal and lateral mitral annulus velocities (e') were measured using tissue Doppler, all in the apical 4-chamber view. TTE images were later reported by a second cardiologist, blinded to the invasive measurements and the patient. Correlations between E; E/A ratio; E/e' ratio and PCWP were evaluated using Pearson's correlation. Results Sixty patients were recruited into the study, aged 58±14 years, 27% female, with 96 assessments undertaken. The majority (55%) of patients were SCAI stage C, with 14% having had a cardiac arrest prior to CICU admission and 27% required mechanical ventilation at the time of assessment. Mean PCWP was 16.0±6.5 mmHg. Full mitral valve Doppler and tissue Doppler profiles were measured in 67 (70%) assessments, limited due to E/A fusion, atrial fibrillation and limited acoustic windows. There was only weak correlation between PCWP and E/A ratio (R=0.33, p=0.01), with no correlation between PCWP and the other measured values (Table 1), including E/e'. The AUC for identifying patients with elevated PCWP (≥15 mmHg) using E/A ratio was 0.67 (p=0.02), although there was no suitable value to use as a cut off with adequate sensitivity and specificity (Figure 1). Conclusion Echocardiographic non-invasive assessment of left sided cardiac filling pressures is technically challenging in patients with CS. Even when possible, there is weak correlation between echocardiographic and invasive measurements, suggesting limited value in this technique. Alternative non-invasive modalities, such as lung ultrasound, should be investigated in this population to assist clinical assessment. 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.

Diagnosis of Heart Failure With Preserved Ejection Fraction Among Patients With Unexplained Dyspnea

Diagnosis of heart failure with preserved ejection fraction (HFpEF) among dyspneic patients without overt congestion is challenging. Multiple diagnostic approaches have been proposed but are not well validated against the independent gold standard for HFpEF diagnosis of an elevated pulmonary capillary wedge pressure (PCWP) during exercise. To evaluate H2FPEF and HFA-PEFF scores and a PCWP/cardiac output (CO) slope of more than 2 mm Hg/L/min to diagnose HFpEF. This retrospective case-control study included patients with unexplained dyspnea from 6 centers in the US, the Netherlands, Denmark, and Australia from March 2016 to October 2020. Diagnosis of HFpEF (cases) was definitively ascertained by the presence of elevated PCWP during exertion; control individuals were those with normal rest and exercise hemodynamics. Logistic regression was used to evaluate the accuracy of HFA-PEFF and H2FPEF scores to discriminate patients with HFpEF from controls. Among 736 patients, 563 (76%) were diagnosed with HFpEF (mean [SD] age, 69 [11] years; 334 [59%] female) and 173 (24%) represented controls (mean [SD] age, 60 [15] years; 109 [63%] female). H2FPEF and HFA-PEFF scores discriminated patients with HFpEF from controls, but the H2FPEF score had greater area under the curve (0.845; 95% CI, 0.810-0.875) compared with the HFA-PEFF score (0.710; 95% CI, 0.659-0.756) (difference, -0.134; 95% CI, -0.177 to -0.094; P < .001). Specificity was robust for both scores, but sensitivity was poorer for HFA-PEFF, with a false-negative rate of 55% for low-probability scores compared with 25% using the H2FPEF score. Use of the PCWP/CO slope to redefine HFpEF rather than exercise PCWP reclassified 20% (117 of 583) of patients, but patients reclassified from HFpEF to control by this metric had clinical, echocardiographic, and hemodynamic features typical of HFpEF, including elevated resting PCWP in 66% (46 of 70) of reclassified patients. In this case-control study, despite requiring fewer data, the H2FPEF score had superior diagnostic performance compared with the HFA-PEFF score and PCWP/CO slope in the evaluation of unexplained dyspnea and HFpEF in the outpatient setting.

Transvenous Right Greater Splanchnic Nerve Ablation in Heart Failure and Preserved Ejection Fraction: First-in-Human Study

BackgroundAblation of the right-sided greater splanchnic nerve (GSN) can reduce excessive splanchnic vasoconstriction, potentially improving the handling of volume shifts in patients with heart failure with preserved ejection fraction (HFpEF). ObjectivesThe purpose of this study was to assess a novel catheter procedure of right-sided GSN ablation to treat HFpEF: splanchnic ablation for volume management. MethodsThis trial included 11 HFpEF patients (8 women, age 70 ± 8 years) with New York Heart Association functional class II or III symptoms, ejection fraction ≥50%, and elevated pulmonary capillary wedge pressure at rest or with exercise. After splanchnic ablation for volume management, follow-up at 1, 3, 6, and 12 months included 6-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ), and echocardiography. ResultsThere were no device-related adverse cardiac events or clinical sequelae following right GSN ablation through 12 months. Patients experienced clinical improvements by 1 month that were sustained through 12 months. KCCQ score improved from baseline median 48 (IQR: 35-52) to 65 (IQR: 58-77) at 1 month and 80 (IQR: 77-88) at 12 months (P < 0.05). The 6-minute walk test distance increased from baseline 292 ± 82 m to 341 ± 88 m at 1 month and 359 ± 75 m at 12 months (P < 0.05). The NT-proBNP decreased from a baseline mean of 1,292 ± 1,186 pg/mL to 1,202 ± 797 pg/mL (P = 0.585) at 1 month, to 472 ± 226 pg/mL (P = 0.028) at 6 months, and to 379 ± 165 pg/mL (P = 0.039) at 12 months. ConclusionsIn this open-label, single-arm feasibility study, right-sided GSN ablation was safe and improved mostly subjective clinical metrics in patients with HFpEF over 12 months. (Endovascular GSN Ablation in Subjects With HFpEF; NCT04287946)