Exercise Blood Pressure in Heart Failure With Preserved and Reduced Ejection Fraction.

OBJECTIVES: This study aimed to evaluate hemodynamic correlates of inducible blood pressure (BP) pulsatility with exercise in heart failure with preserved ejection fraction (HFpEF), to identify relationships to outcomes, and to compare this with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: In HFpEF, determinants and consequences of exercise BP pulsatility are not well understood. METHODS: We measured exercise BP in 146 patients with HFpEF who underwent invasive cardiopulmonary exercise testing. Pulsatile BP was evaluated as proportionate pulse pressure (PrPP), the ratio of pulse pressure to systolic pressure. We measured pulmonary arterial catheter pressures, Fick cardiac output, respiratory gas exchange, and arterial stiffness. We correlated BP changes to central hemodynamics and cardiovascular outcome (nonelective cardiovascular hospitalization) and compared findings with 57 patients with HFrEF from the same referral population. RESULTS: In HFpEF, only age (standardized beta = 0.593; P < 0.001), exercise stroke volume (standardized beta = 0.349; P < 0.001), and baseline arterial stiffness (standardized beta = 0.182; P = 0.02) were significant predictors of peak exercise PrPP in multivariable analysis (R = 0.661). In HFpEF, lower PrPP was associated with lower risk of cardiovascular events, despite adjustment for confounders (HR:0.53 for PrPP below median; 95% CI: 0.28-0.98; P = 0.043). In HFrEF, lower exercise PrPP was not associated with arterial stiffness but was associated with lower peak exercise stroke volume (P = 0.013) and higher risk of adverse cardiovascular outcomes (P = 0.004). CONCLUSIONS: In HFpEF, greater inducible BP pulsatility measured using exercise PrPP reflects greater arterial stiffness and higher risk of adverse cardiovascular outcomes, in contrast to HFrEF where inducible exercise BP pulsatility relates to stroke volume reserve and favorable outcome.

Metabolic Cost of Exercise Initiation in Patients With Heart Failure With Preserved Ejection Fraction vs Community-Dwelling Adults.

Importance: Heart failure with preserved ejection fraction (HFpEF) is a joint metabolic and cardiovascular disorder with significant noncardiac contributions. Objective: To define and quantify the metabolic cost of initiating exercise in individuals with and without HFpEF and its functional consequences. Design, Setting, and Participants: This prospective cohort study included individuals with hemodynamically confirmed HFpEF from the Massachusetts General Hospital Exercise Study (MGH-ExS) and community-dwelling participants from the Framingham Heart Study (FHS). Analysis began April 2016 and ended November 2020. Exposures: Internal work (IW), a measure of work equivalents required to initiate movement. Main Outcomes and Measures: Using breath-by-breath oxygen uptake (V̇o2) measurements and V̇o2-work rate associations, cost of initiating exercise (IW) in patients with HFpEF (MGH-ExS) and in community-dwelling individuals (FHS) was quantified. Linear regression was used to estimate associations between IW and clinical/hemodynamic measures. Results: Of 3231 patients, 184 (5.7%) had HFpEF and were from MGH-ExS, and 3047 (94.3%) were community-dwelling individuals from FHS. In the MGH-ExS cohort, 86 (47%) were women, the median (interquartile range) age was 63 (53-72) years, and the median (interquartile range) peak V̇o2 level was 13.33 (11.77-15.62) mL/kg/min. In the FHS cohort, 1620 (53%) were women, the median (interquartile range) age was 54 (48-60) years, and the median (interquartile range) peak V̇o2 level was 22.2 (17.85-27.35) mL/kg/min. IW was higher in patients with HFpEF and accounted for 27% (interquartile range, 21%-39%) of the total work (IW + measured external workload on the cycle), compared with 15% (interquartile range, 12%-20%) of that in FHS participants. Body mass index accounted for greatest explained variance in patients with HFpEF from MGH-ExS and FHS participants (22% and 18%, respectively), while resting cardiac output and biventricular filling pressures were not significantly associated with variance in IW in patients with HFpEF. A higher IW in patients with HFpEF was associated with a greater increase in left- and right-sided cardiac filing pressure during unloaded exercise, despite similar resting hemodynamic measures across IW. Conclusions and Relevance: This study found that internal work, a new body mass index-related measure reflecting the metabolic cost of initiating movement, is higher in individuals with HFpEF compared with middle-aged adults in the community and is associated with steep, early increases in cardiac filling pressures. These findings highlight the importance of quantifying heterogeneous responses to exercise initiation when evaluating functional intolerance in individuals at risk for or with HFpEF.

Pulmonary Capillary Wedge Pressure Patterns During Exercise Predict Exercise Capacity and Incident Heart Failure.

BACKGROUND: Single measurements of left ventricular filling pressure at rest lack sensitivity for identifying heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea on exertion. We hypothesized that exercise hemodynamic measurements (ie, changes in pulmonary capillary wedge pressure [PCWP] indexed to cardiac output [CO]) may more sensitively differentiate HFpEF and non-HFpEF disease states, reflect aerobic capacity, and forecast heart failure outcomes in individuals with normal PCWP at rest. METHODS AND RESULTS: We studied 175 patients referred for cardiopulmonary exercise testing with hemodynamic monitoring: controls (n=33), HFpEF with resting PCWP≥15 mm Hg (n=32), and patients with dyspnea on exertion with normal resting PCWP and left ventricular ejection fraction (DOE-nlrW; n=110). Across 1835 paired PCWP-CO measurements throughout exercise, we used regression techniques to define normative bounds of "PCWP/CO slope" in controls and tested the association of PCWP/CO slope with exercise capacity and composite cardiac outcomes (defined as cardiac death, incident resting PCWP elevation, or heart failure hospitalization) in the DOE-nlrW group. Relative to controls (PCWP/CO slope, 1.2±0.4 mm Hg/L/min), patients with HFpEF had a PCWP/CO slope of 3.4±1.9 mm Hg/L/min. We used a threshold (2 SD above the mean in controls) of 2 mm Hg/L/min to define abnormal. PCWP/CO slope >2 in DOE-nlrW patients was common (n=45/110) and was associated with reduced peak Vo2 (P<0.001) and adverse cardiac outcomes after adjustment for age, sex, and body mass index (hazard ratio, 3.47; P=0.03) at a median 5.3-year follow-up. CONCLUSIONS: Elevated PCWP/CO slope during exercise (>2 mm Hg/L/min) is common in DOE-nlrW and predicts exercise capacity and heart failure outcomes. These findings suggest that current definitions of HFpEF based on single measures during rest are insufficient and that assessment of exercise PCWP/CO slope may refine early HFpEF diagnosis.

Detecting letters and words in prose passages: a test of alternative theoretical accounts of the missing letter effect.

College students searched for either h or the in prose passages in which every h occurred in the test word the. In Experiment 1, passage versions differed in that the critical noun phrases were either the alone (i.e., in citation form as a noun referring to itself) or "the definite article." Many more detection errors occurred for letter than word target items, especially with "the definite article." In Experiment 2, passage versions differed in that a given noun phrase containing the test word the occurred as a subject in one version and an object in the other. Again, many more detection errors occurred when the target item was the letter h than when it was the letter sequence the. Also, with letter but not letter sequence targets, more detection errors occurred for object than subject noun phrases. In Experiment 3, passages were presented either in regular format or with all capital letters. Students made more detection errors with the regular than with the capitals format, many more errors occurred when participants searched for letters than for letter sequences, and the effect of target item was larger with regular than with capitals format. These findings suggest that accounts of detection errors in reading must include the influence of unitization and processing time or attentional allocation.

Short-term recall of order information: influence of encoding and generation processes on distinctiveness, isolation, and background effects.

We examined the influence of encoding and generation processes on distinctiveness, isolation, and background effects in short-term recall of order information. Adults recalled the order of letters in one of two segments following a distractor task, knowing in advance the identity of the letters. A distinctive letter was one that was either in red or absent and replaced with a red dash, thereby requiring generation. On trials with a distinctive letter, the letter was primed in advance. A negative generation effect was found; in addition, there was a positive distinctiveness effect but a negative background effect on trials in which generation was required. These effects can be explained in terms of the extra processing given to distinctive items when they need to be generated.

Reading units that include interword spaces: filling spaces around a letter can facilitate letter detection.

College students searched for the letter "a" in prose passages typed normally, with an asterisk (Experiments 1 and 2) or the letter "x" (Experiment 3) replacing every interword space, or with asterisks replacing only some of the interword spaces (Experiment 2). Contrary to predictions based on masking through lateral interference but consistent with predictions based on studies of eye movement monitoring and unitization, asterisks or instances of the letter "x" surrounding the word "a" actually made the letter "a" easier to detect in that word, but generally not in other words in the text. It is concluded that for very common words, reading units may extend beyond the word boundary to include the surrounding interword spaces.

Encoding and output order processes in short-term order recall of distinctive items.

Adults recalled the order of the letters in one of two four-letter segments following a distractor task. They knew in advance the identity of the letters in each segment. A letter was made distinctive by replacing it with a red dash. This unusual form of distinctiveness generally had negative effects on recall of both the segment containing the missing letter and the absent letter within the segment. Encoding and output processes were manipulated by varying precue information and recall order instructions, respectively. Informing participants in advance whether or not a trial would contain a distinctive (i.e., missing) letter depressed recall. Constraining output order eliminated the disadvantage for the absent letter. The results are discussed in terms of encoding and output order processes in short-term recall of order information.