Feasibility of Noninvasive Assessment of Cardiac Output during Exercise in Healthy Adults by a Novel Elaboration on Systolic Time Intervals.

BACKGROUND: Although assessment of cardiovascular hemodynamics during exercise can provide clinical insights, it is challenging to acquire it in clinical settings. OBJECTIVES: Accordingly, this preliminary study was to determine whether a novel elaboration on systolic time interval measures (eSTICO) method of quantifying cardiac output and stroke volume was comparable to those obtained using a validated soluble gas (open circuit CO measure [OpCircCO]) method or calculation based on oxygen consumption (oxygen consumption-based CO [VO2CO]) during exercise. METHODS: For the present study, 14 healthy subjects (male: n = 12, female: n = 2) performed incremental exercise on a recumbent cycle ergometer. At rest and during exercise, cardiac output (CO) was obtained via the eSTICO method, while the OpenCircCO and VO2CO measures were obtained at the last minute of each workload. RESULTS: At peak, there was no difference between eSTICO and OpCircCO (12.39 ± 3.06 vs. 13.96 ± 2.47 L/min, p > 0.05), while there was a slight difference between eSTICO and VO2CO (12.39 ± 3.06 vs. 14.28 ± 2.55 L/min, p < 0.05). When we performed correlation analysis with all subjects and all measures of CO at all WL, between eSTICO and OpenCircCO, there was a good relationship (r = 0.707, p < 0.001) with a Bland and Altman agreement analysis demonstrating a -1.6 difference (95% LoA: -6.3-3.5). Between eSTICO and VO2CO, we observed an r = 0.865 (p < 0.001) and a Bland and Altman agreement analysis with a -1.2 difference (95% LoA: -4.8-2.4). CONCLUSION: A novel exploitation of cardiac hemodynamics using systolic timing intervals may allow a relatively good assessment of CO during exercise in healthy adults.

Hemodynamic Assessment in Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by an inability of the heart to perfuse the body without pathologic increases in filling pressure at rest or during exertion. Right heart catheterization provides direct assessment for HF, providing the most robust and direct method to evaluate the central hemodynamic abnormalities, and serves as the gold standard to confirm or refute the presence of HFpEF. This article reviews current understanding of the best practices in the performance and interpretation of hemodynamic assessment, relates important pathophysiologic concepts to clinical care, and discusses current and evidence-based applications of hemodynamics in HFpEF.

Application of Guideline-Based Echocardiographic Assessment of Left Atrial Pressure to Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Early, noninvasive identification of patients with heart failure with preserved ejection fraction (HFpEF) with congestion may allow timely tailoring of decongestive therapies. The 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines provide an algorithm to assess for elevated left atrial pressure (LAP); the associations of echocardiographic LAP with clinical status and disease progression in patients with HFpEF are unclear. METHODS: Participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial were categorized into one of four prespecified guideline-based echocardiographic LAP categories: (1) normal, (2) elevated, (3) atrial fibrillation (AF) at the time of echocardiography, or (4) indeterminate. Associations of echocardiographic LAP categories with baseline exercise capacity, change in exercise capacity, and change in N-terminal pro-B-type natriuretic peptide over 24 weeks were evaluated. RESULTS: Of 216 participants, 199 underwent mitral inflow Doppler echocardiography for LAP categorization. Participants with elevated echocardiographic LAP (n = 81) or AF (n = 57) were older and had a higher prevalence of kidney dysfunction. Compared with the normal echocardiographic LAP group (n = 28), elevated echocardiographic LAP and AF were each independently associated with a greater reduction in peak oxygen consumption over 24 weeks after adjusting for baseline values and clinical covariates (ß for elevated echocardiographic LAP = -1.55 [95% CI, -2.59 to -0.51], P = .004; ß for AF = -1.33 [95% CI, -2.49 to -0.17], P = .03). Indeterminate echocardiographic LAP (n = 33) was also independently associated with a reduction in exercise capacity at 24 weeks compared with normal echocardiographic LAP (ß = -1.35; 95% CI, -2.51 to -0.19; P = .02). Finally, elevated echocardiographic LAP and AF were significantly associated with increases in N-terminal pro-B-type natriuretic peptide over 24 weeks compared with normal echocardiographic LAP. CONCLUSIONS: In patients with chronic HFpEF, elevated echocardiographic LAP and indeterminate echocardiographic LAP, as defined by contemporary guidelines, and AF were each independently associated with a reduction in exercise capacity compared with normal echocardiographic LAP. These findings suggest the potential utility of noninvasive LAP assessment in patients with HFpEF for tailoring treatments that decrease congestion.

Hemodynamic assessment in heart failure.

Hemodynamics play a central role in the pathophysiology of heart failure (HF), yet their proper assessment and optimization remains challenging. Heart failure is defined as the inability of the heart to deliver adequate perfusion (cardiac output) to the body at rest or exercise, or to require an elevation in cardiac filling pressures in order to do this. This bedrock definition is important because it relies on measurable quantities (filling pressures and output) that are readily assessed in the cardiac catheterization laboratory. Here we present three cases to illustrate how better understanding of the determinants of cardiac output and stroke volume: preload, afterload, contractility, and lusitropy, as well as the determinants of congestion (high filling pressures) may be used to guide optimization of hemodynamic status. The goal is that the readers will be able to think more critically when evaluating the hemodynamics of their patient in HF and recognize the complex interplay that determines the complex balance between cardiac ejection and filling capabilities, and how this alters symptoms and outcomes for patients with HF. KEY POINTS: Careful assessment of hemodynamics in the catheterization laboratory allows for actionable insight to a patient's volume status, cardiac function and can help prognosticate outcomes. Exercise hemodynamics in heart failure is a powerful tool to better understand the cause of symptoms and predict outcomes. Clinicians should aim to decrease biventricular filling pressures to normal values to improve morbidity and reduce risk for readmission. In patients with heart failure and reduced ejection fraction, clinicians should aim to decrease afterload as much as can be tolerated by the renal function and patient's symptoms. Low cardiac output can often be improved by optimizing preload and afterload rather than initiating inotropes, which should be reserved until needed. In advanced heart failure, the right heart function becomes a key determinant of symptoms and outcomes.

Assessment of Predictors of Left Atrial Volume Response to a Transcatheter InterAtrial Shunt Device (from the REDUCE LAP-HF Trial).

In patients with heart failure and preserved or mildly reduced ejection fractions (EF ≥40%), implantation of an interatrial shunt device (IASD) resulted in heterogenous changes of the left atrial (LA) volume. Baseline characteristics that correlate with a favorable decrease in LA volume are unknown. We hypothesized that a larger ratio of left to right atrial volume at baseline would correlate strongly with LA volume decongestion following IASD implantation. Reduce Elevated LA Pressure in Patients With Heart Failure was a multicenter study of the safety and feasibility of IASD implantation. Sixty-four patients with EF ≥40% underwent device implantation along with baseline conventional echocardiograms, speckle tracking echocardiography, and resting and exercise hemodynamics. Higher LA compliance (-4.2%, p = 0.048) and right atrial reservoir strain (-0.8%, p = 0.005) were independently associated with a percent decrease in the systolic LA volume index from baseline to 6-months. In conclusion, greater LA volume reduction following IASD implantation is associated with higher baseline compliance of the left atrium and higher reservoir strain of the right atrium.

Assessment and Implications of Right Ventricular Afterload in Tetralogy of Fallot.

Patients with tetralogy of Fallot (TOF) have abnormal right ventricular (RV) afterload because of residual or recurrent outflow tract obstruction, often with abnormal pulmonary artery (PA) vascular function. The purpose of this study was to determine if RV afterload was independently associated with death and/or heart transplant in patients with TOF. This is a retrospective study of TOF patients that underwent cardiac catheterization for clinical indications at Mayo clinic between 1990 and 2015. Invasively measured RV systolic pressure (RVSP) was used to define RV afterload. To explore clinical utility for echocardiographic estimates of invasive data, correlations between invasive and Doppler-derived indices of RV afterload were examined. Among 266 patients with TOF (age 35 ± 14 years, TOF-pulmonary atresia 117 [44%]), RVSP was 72 ± 28 mm Hg, PA systolic pressure 45 ± 19 mm Hg, mean PA pressure 27 ± 10 mm Hg, pulmonary vascular resistance 4.2 ± 3.1 WU, and PA wedge pressure 14 ± 5 mm Hg. Over a mean follow up of 12.9 years, there were 35 deaths and 4 heart transplants. Invasively measured RVSP (hazard ratio 1.25, 95% confidence interval 1.12 to 1.37; p <0.001) and TOF-pulmonary atresia (hazard ratio 1.18, 95% confidence interval 1.08 to 1.41; p = 0.023) were independent risk factors for death and/or transplant. Doppler-derived RVSP was well-correlated with invasive RVSP (r = 0.92, p <0.001), and was also independently associated with the combined end point. RVSP, a composite measure of RV afterload, is independently prognostic in patients with TOF, and can be reliably assessed using Doppler echocardiography. Further study is required to test whether interventions to reduce RVSP can improve outcomes in patients with TOF.

Assessment of Right Ventricular-Pulmonary Arterial Coupling in Chronic Pulmonary Regurgitation.

BACKGROUND: We hypothesized that noninvasively measured right ventricular (RV) to pulmonary arterial (RV-PA) coupling would be abnormal in chronic pulmonary regurgitation (PR) even in the setting of normal RV ejection fraction, and that RV-PA coupling indices would have a better correlation with peak oxygen consumption (VO2) compared with RV systolic indices alone. METHODS: This was a retrospective study of 129 adults (repaired tetralogy of Fallot [TOF] n = 84 and valvular pulmonic stenosis [VPS] with previous intervention n = 45) with ≥ moderate native PR and RV ejection fraction > 50%. The 84 TOF patients were propensity matched with 84 patients with normal echocardiogram (control); age 28 ± 7 years and male sex n = 39 (46%). RV-PA coupling was measured according to fractional area change (FAC)/RV systolic pressure (RVSP) and tricuspid annular plane systolic excursion (TAPSE)/RVSP. RESULTS: RV systolic function indices were similar between TOF and control groups (FAC 43 ± 6% vs 41 ± 5% [P = 0.164] and TAPSE 22 ± 5 mm vs 24 ± 6 mm [P = 0.263]). However, RV-PA coupling was lower in the TOF group (FAC/RVSP 1.10 ± 0.29 vs 1.48 ± 0.22 [P < 0.001]; TAPSE/RVSP 0.51 ± 0.15 vs 0.78 ± 0.11 [P < 0.001]) because of higher RV afterload (RVSP 42 ± 3 mm Hg vs 31 ± 3 mm Hg [P = 0.012]). FAC/RVSP (r = 0.61; P < 0.001) and TAPSE/RVSP (r = 0.69; P < 0.001) correlated with peak VO2 especially in the patients with impaired exercise capacity whereas FAC and TAPSE were independent of peak VO2. Similar comparisons between VPS and control groups showed no difference in TAPSE and FAC between groups, but lower FAC/RVSP and TAPSE/RVSP in the VPS group. CONCLUSIONS: There is abnormal RV-PA coupling in chronic PR, and noninvasively measured RV-PA coupling might potentially be prognostic because of its correlation with exercise capacity.

Hemodynamic Assessment of Patients With and Without Heart Failure Symptoms Supported by a Continuous-Flow Left Ventricular Assist Device.

OBJECTIVE: To investigate differences in invasive hemodynamic parameters and outcomes in patients with and without heart failure (HF) symptoms after left ventricular assist device (LVAD) implantation. PATIENTS AND METHODS: We performed a single-center retrospective analysis of 51 symptomatic patients and 50 patients with resolved HF symptoms who underwent right-sided heart catheterization (RHC) after LVAD implantation from March 1, 2007, through June 30, 2016. Patient characteristics and outcomes including all-cause mortality and right ventricular (RV) failure were compared between groups. RESULTS: Fifty-one patients had development of HF symptoms after LVAD implantation and underwent RHC a mean ± SD of 243.7±288 days postoperatively. Fifty asymptomatic LVAD recipients underwent routine RHC 278.6±205 days after implantation. Compared with patients who had resolved HF symptoms, symptomatic patients were older, more likely to be male, and more likely to have ischemic cardiomyopathy. Symptomatic patients had higher right atrial pressure (P<.001), mean pulmonary arterial pressure (P<.001), and pulmonary capillary wedge pressure (P<.001). Improvements in right atrial pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure before and after LVAD implantation were less remarkable in symptomatic patients. The frequency of RV dysfunction was significantly higher among symptomatic patients than patients with resolved HF symptoms (P=.001). Symptomatic patients displayed significantly higher risk of all-cause mortality (hazard ratio, 3.0; 95% CI, 1.3-6.5; P=.007) and RV failure (hazard ratio, 6.2; 95% CI, 1.3-29.7; P=.02) independent of other predictors of outcome. CONCLUSION: Patients with recurrent HF symptoms after LVAD implantation display more profound hemodynamic derangements, greater burden of RV failure, and increased rates of all-cause mortality compared with LVAD recipients with resolved HF symptoms.

Invasive and noninvasive hemodynamic assessment in adults with Fontan palliation.

BACKGROUND/OBJECTIVES: Although echocardiographic-Doppler cardiac index (CI) assessment is widely used to guide heart failure management in patients with biventricular circulation, this application has not been studied in the Fontan population. The objective of this study was to: (1) determine the correlation between Doppler and cardiac catheterization CI calculation; (2) determine the association between Doppler CI and the occurrence of Fontan failure. METHODS: Retrospective review of adult Fontan patients followed at Mayo Clinic Adult Congenital Heart Disease program, 1994-2015. Inclusion criteria were: systemic left ventricle and echocardiogram and cardiac catheterization performed within the same week. Fontan failure was defined as a composite of all-cause mortality, heart transplantation listing, and palliative care. RESULTS: 59 patients (age 29±6years; men 32[54%]) underwent 97 studies. Of the 59, 41[69%] had atriopulmonary Fontan and 12 (20%) had cirrhosis. Compared to patients without cirrhosis, patients with cirrhosis had higher Doppler CI (3.6±0.6 vs 2.8±0.4L/min∗m2, p=0.039); Fick CI (3.3 [2.5-3.7] vs 2.4 [1.6-3.1] L/min/m2, p=0.028); lower systemic vascular resistance (20±3 vs 25±4 WU∗m2, p=0.04). There was a positive correlation between Doppler and Fick CI (r=0.52; p<0.0001). Fontan failure occurred in 13 patients (22%) within 7.5±2.1years. In patients without cirrhosis, Fick CI and Doppler CI <2.5L/min/m2 were associated with Fontan failure (odds ratio [OR] 1.58, p=0.046) and (OR 1.43, p=0.051) respectively. CONCLUSIONS: Doppler CI assessment in feasible in a selected group of Fontan patients and it is predictive of clinical outcomes. The application of this concept in systemic right ventricles deserves further research.

Pulmonary Pressure Assessment with the Total Artificial Heart.

Reversal of pulmonary hypertension has been observed in patients during a bridge to transplant with a left ventricular assist device. Total artificial heart (TAH) implant prevents subsequent right heart catheterization. Consequently, controversy exists over whether the prosthetic right ventricle improves or exacerbates pulmonary hypertension. A pulmonary artery (PA) pressure monitor was placed in two patients undergoing TAH implant, as a bridge to transplant. One patient had pulmonary hypertension at implant; the other had normal pulmonary pressures. Daily measurements were taken of systolic, diastolic, and mean PA pressures throughout support. Patient 1 received successful transplant after TAH support of 91 days. Systolic/diastolic (mean) PA pressures steadily decreased from 55/39 (28) mm Hg at implant to 29/18 (7) mm Hg currently. Patient 2 received support for 101 days before death due to abdominal ischemic complications. Pulmonary arterial pressures stayed consistent throughout this period, from 26/17 (20) mm Hg at implant to 23/13 (17) mm Hg at the time of death. These findings suggest that an implantable PA pressure monitor may be useful in optimizing hemodynamics and planning appropriate timing of transplant with TAH support.

Why are women more likely than men to develop heart failure with preserved ejection fraction?

PURPOSE OF REVIEW: Women are approximately two times more likely than men to develop heart failure in the setting of preserved left ventricular ejection fraction [i.e. heart failure with preserved left ventricular ejection fraction (HFpEF)], but the reasons for this disparity are unknown. RECENT FINDINGS: HFpEF is caused by changes in ventricular-vascular properties that are associated with aging and hypertensive cardiac remodeling. These changes lead to diastolic and systolic dysfunction and impaired reserve capacity. Many of the cardiovascular alterations seen in HFpEF are also noted to greater extent in women compared with men. Women demonstrate more concentric left ventricular remodeling and less ventricular dilatation in response to arterial hypertension. Ventricular and arterial stiffness increases with age in both sexes, but the increase is more dramatic in women. Recently, age-sex interactions have also been observed in the manner in which left ventricular function changes across the lifespan, wherein systolic and diastolic function and functional reserve become more compromised in women as compared with men in the postmenopausal years, despite similar or enhanced function in women during youth. SUMMARY: The prevalence of HFpEF is increasing and women outnumber men by a 2 : 1 ratio. Recent data have identified striking parallels between structure-function alterations observed in HFpEF and sex differences in cardiovascular function across the adult lifespan. These data suggest that sex-specific maladaptations to hypertensive aging in women may underlie greater risk of HFpEF.

Bedside assessment of cardiac hemodynamics: the impact of noninvasive testing and examiner experience.

BACKGROUND: Knowledge of cardiac filling pressures is critical in the diagnosis and management of patients with dyspnea or heart failure. Echocardiography and B-natriuretic peptide (BNP) testing are commonly used to estimate these pressures, but their incremental value beyond physical examination remains unknown. METHODS: Right and left heart filling pressures were prospectively estimated as "normal" or "abnormal" by staff cardiologists and cardiovascular trainees based upon physical examination findings alone, or examination coupled with echocardiographic and BNP data in patients referred for cardiac catheterization. Net reclassification improvement was calculated to determine whether echocardiographic/BNP data had incremental value in the determination of right and left heart pressures. RESULTS: Two hundred fifteen observations were made by 9 examiners in 116 consecutive patients. Right and left heart pressures were accurately predicted from examination alone in 71% and 60% of observations, respectively. Examination-based accuracy was greater for staff cardiologists compared with trainees for right heart (82 vs 67%, P=.03) and left heart pressures (71% vs 55%, P=.03). Exposure to echocardiographic and BNP data did not enhance accuracy beyond bedside examination alone, both for left heart pressures (net reclassification improvement=-0.004; 95% confidence interval, -0.12-0.12) and right heart pressures (net reclassification improvement=0.02, 95% confidence interval, -0.09-0.13). CONCLUSIONS: Cardiac filling pressures can be estimated from physical examination with modest accuracy, which is enhanced with experience. While echocardiographic and BNP data predict cardiac filling pressures, they may not provide information of incremental value beyond examination alone. Rigorous teaching and practice of cardiac examination skills should continue to be emphasized during medical training.

Invasive hemodynamic assessment in heart failure.

Routine cardiac catheterization provides data on left heart, right heart, systemic and pulmonary arterial pressures, vascular resistances, cardiac output, and ejection fraction. These data are often then applied as markers of cardiac preload, afterload, and global function, although each of these parameters reflects more complex interactions between the heart and its internal and external loads. This article reviews more specific gold standard assessments of ventricular and arterial properties, and how these relate to the parameters reported and utilized in practice, and then discusses the re-emerging importance of invasive hemodynamics in the assessment and management of heart failure.

Invasive hemodynamic assessment in heart failure.

Routine cardiac catheterization provides data on left heart, right heart, systemic and pulmonary arterial pressures, vascular resistances, cardiac output, and ejection fraction. These data are often then applied as markers of cardiac preload, afterload, and global function, although each of these parameters reflects more complex interactions between the heart and its internal and external loads. This article reviews more specific gold standard assessments of ventricular and arterial properties, and how these relate to the parameters reported and utilized in practice, and then discusses the re-emerging importance of invasive hemodynamics in the assessment and management of heart failure.

Severe heart failure in the setting of relatively mild mitral stenosis: the role of invasive hemodynamic assessment.

For patients with heart failure and relatively mild mitral stenosis, an exercise hemodynamic study should be considered. However, exercise intolerance is a common symptom in a variety of cardiac and noncardiac diseases, emphasizing the need for a thorough differential diagnosis in the planning and execution of these studies. This manuscript discusses two cases that illustrate the need for this comprehensive approach, the indications for balloon mitral valvuloplasty, and the recognition of diastolic dysfunction in these patients.