Pulmonary hypertension (PH) is frequent in left heart disease (LHD), as a consequence of the underlying condition. Significant advances have occurred over the past 5 years since the 5th World Symposium on Pulmonary Hypertension in 2013, leading to a better understanding of PH-LHD, challenges and gaps in evidence. PH in heart failure with preserved ejection fraction represents the most complex situation, as it may be misdiagnosed with group 1 PH. Based on the latest evidence, we propose a new haemodynamic definition for PH due to LHD and a three-step pragmatic approach to differential diagnosis. This includes the identification of a specific “left heart” phenotype and a non-invasive probability of PH-LHD. Invasive confirmation of PH-LHD is based on the accurate measurement of pulmonary arterial wedge pressure and, in patients with high probability, provocative testing to clarify the diagnosis. Finally, recent clinical trials did not demonstrate a benefit in treating PH due to LHD with pulmonary arterial hypertension-approved therapies.

https://erj.ersjournals.com/content/erj/53/1/1801897.full.pdf

Pulmonary hypertension due to left heart disease.

Background: Accurate measurement of left ventricular filling pressure (LVEDP) is important to distinguish between Group 1 pulmonary arterial hypertension (PAH) and Group 2 pulmonary hypertension from diastolic heart failure (PH-HFpEF). Methods: We prospectively performed cardiac catheterization on 62 patients referred for evaluation of PH and compared the LVEDP at end-expiration to: a) the pulmonary capillary wedge pressure manually determined at end-expiration (PCWP-EXP) and b) the PCWP determined electronically (PCWP-digital). Results: The PCWP-EXP was a more reliable measure of the LVEDP (mean 13mmHg vs 12.4mmHg, p=NS) than the PCWP-digital (mean 8mmHg vs 12.4mmHg, p Conclusions: The common practice of using PCWP-digital measurements instead of PCWP-EXP measurements results in significant underestimation of the LVEDP. In our study, this translated to almost 20% of patients being misclassified as having PAH rather than PH-HFpEF. Thus, reliance on PCWP-digital measurements should be avoided as this may lead to the inappropriate use of pulmonary vasodilators.

Current practice for determining pulmonary capillary wedge pressure predisposes to serious errors in the classification of patients with pulmonary hypertension

Background The cardiopulmonary haemodynamic profile observed during exercise may identify patients with early-stage pulmonary vascular and primary cardiac diseases, and is used clinically to inform prognosis. However, a standardised approach to interpreting haemodynamic parameters is lacking. Methods We performed a systematic literature search according to PRISMA guidelines to identify parameters that may be diagnostic for an abnormal haemodynamic response to exercise and offer optimal prognostic and differential-diagnostic value. We performed random-effects meta-analyses of the normal values and report effect sizes as weighted mean±sd. Results of diagnostic and prognostic studies are reported descriptively. Results We identified 45 eligible studies with a total of 5598 subjects. The mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope, pulmonary arterial wedge pressure (PAWP)/CO slope and peak cardiac index (or CO) provided the most consistent prognostic haemodynamic parameters during exercise. The best cut-offs for survival and cardiovascular events were a mPAP/CO slope >3 Wood units (WU) and PAWP/CO slope >2 WU. A PAWP/CO slope cut-off >2 WU best differentiated pre- from post-capillary causes of PAP elevation during exercise. Upper limits of normal (defined as mean+2sd) for the mPAP/CO and PAWP/CO slopes were strongly age-dependent and ranged in 30–70-year-old healthy subjects from 1.6 to 3.3 WU and 0.6 to 1.8 WU, respectively. Conclusion An increased mPAP/CO slope during exercise is associated with impaired survival and an independent, prognostically relevant cut-off >3 WU has been validated. A PAWP/CO slope >2 WU may be suitable for the differentiation between pre- and post-capillary causes of PAP increase during exercise. Elevated mPAP/CO slope is associated with impaired survival and an independent, prognostically relevant cut-off >3 WU has been validated. A PAWP/CO slope >2 WU may be suitable for identifying post-capillary causes of PAP increase during exercise. https://bit.ly/3tgVVMB

Diagnostic, prognostic and differential-diagnostic relevance of pulmonary haemodynamic parameters during exercise: a systematic review

Rationale: Current methods assessing clinical risk because of exercise intolerance in patients with cardiopulmonary disease rely on a small subset of traditional variables Alternative strategies incorporating the spectrum of factors underlying prognosis in at-risk patients may be useful clinically, but are lacking Objective: Use unbiased analyses to identify variables that correspond to clinical risk in patients with exercise intolerance Methods and Results: Data from 738 consecutive patients referred for invasive cardiopulmonary exercise testing at a single center (2011–2015) were analyzed retrospectively (derivation cohort) A correlation network of invasive cardiopulmonary exercise testing parameters was assembled using |r|>05 From an exercise network of 39 variables (ie, nodes) and 98 correlations (ie, edges) corresponding to P −46 for each correlation, we focused on a subnetwork containing peak volume of oxygen consumption (pVo 2 ) and 9 linked nodes K-mean clustering based on these 10 variables identified 4 novel patient clusters characterized by significant differences in 44 of 45 exercise measurements ( P 2 and pVo 2 itself, the network model was less redundant and identified clusters that were more distinct Cluster assignment from the network model was predictive of subsequent clinical events For example, a 43-fold ( P P =00018; 95% CI, 15–52) increase in hazard for age- and pVo 2 -adjusted all-cause 3-year hospitalization, respectively, were observed between the highest versus lowest risk clusters Using these data, we developed the first risk-stratification calculator for patients with exercise intolerance When applying the risk calculator to patients in 2 independent invasive cardiopulmonary exercise testing cohorts (Boston and Graz, Austria), we observed a clinical risk profile that paralleled the derivation cohort Conclusions: Network analyses were used to identify novel exercise groups and develop a point-of-care risk calculator These data expand the range of useful clinical variables beyond pVo 2 that predict hospitalization in patients with exercise intolerance

Network Analysis to Risk Stratify Patients With Exercise Intolerance.

BACKGROUND We sought to investigate left atrial (LA) volume, function, and strain in elite athletes by a meta-analysis including echocardiographic studies that provided volumetric and strain analysis of LA phasic function. METHODS The OVID-MEDLINE, PubMed, and Cochrane CENTRAL databases were searched for English-language articles without time restriction up to February 2018 through focused and high sensitive search strategies. Studies were identified by crossing the following search terms: "athletes," "left atrial size," "left atrial volume," "atrial function," "atrial strain," "atrial strain rate," "echocardiography," "2D speckle echocardiography." RESULTS Meta-analysis included 403 athletes and 314 active but not trained healthy controls from 9 studies. Pooled data showed that average LA volume index was higher in athletes than in healthy controls (28.0 ± 1.0 vs 20.7 ± 0.8 mL/m2 , P < 0.001). Global LA longitudinal strain, showing LA reservoir function, was lower in the athletes than in healthy controls with borderline significance (37.0 ± 1.2 vs 38.3 ± 1.5%, P = 0.044). Late diastolic LA strain rate, resembling LA contractile function, was also lower in elite athletes than in control group (-1.56 ± 0.08 vs -1.74 ± 0.09 seconds -1, P = 0.007). CONCLUSIONS Our meta-analysis shows that LA volume is higher, while LA reservoir and contractile functions are impaired in elite athletes during active training compared to untrained controls. Whether these changes persist during deconditioning periods remains to be determined. These alterations may be related to the higher risk of arrhythmias, in particular atrial fibrillation, reported among middle/old aged athletes.

Left atrial function in elite athletes: A meta-analysis of two-dimensional speckle tracking echocardiographic studies.

We studied the contribution of phasic left atrial (LA) function to left ventricular (LV) filling during exercise. We hypothesized that reduced LV filling time at moderate-intensity exercise limits ...

https://www.physiology.org/doi/pdf/10.1152/japplphysiol.00307.2015

Left atrial phasic function interacts to support left ventricular filling during exercise in healthy athletes

The right ventricular (RV)-pulmonary arterial (PA) circulatory unit has not been well studied during prolonged exercise, and this study provides an ecological approach that reflects a typical bout ...

Pulmonary hemodynamic and right ventricular responses to brief and prolonged exercise in middle-aged endurance athletes.

Objectives The clinical and prognostic significance of ‘exaggerated’ elevations in pulmonary artery wedge pressure (PAWP) during symptom-limited exercise testing is increasingly recognised. However, the paucity of normative data makes the identification of abnormal responses challenging. Our objectives was to describe haemodynamic responses that reflect normal adaptation to submaximal exercise in a group of community-dwelling, older, non-dyspnoeic adults. Methods Twenty-eight healthy volunteers (16 men/12 women; 55±6 years) were studied during rest and two consecutive stages of cycle ergometry, at targeted heart rates of 100 bpm (light exercise) and 120 bpm (moderate exercise). Right-heart catheterisation was performed to measure pulmonary artery pressures, both early (2 min) and after sustained (7 min) exercise at each intensity. Results End-expiratory PAWP at baseline was 11±3 mm Hg and increased to 22±5 mm Hg at early-light exercise (p Conclusions The range of PAWP responses to submaximal exercise is broad in health, but also time-variant. PAWP may routinely exceed 20 mm Hg early in exercise. Initial increases in PAWP and mean pulmonary artery pressures do not necessarily reflect abnormal cardiopulmonary physiology, as pressures may normalise within a period of minutes.

https://heart.bmj.com/content/heartjnl/102/6/438.full.pdf

The pulmonary artery wedge pressure response to sustained exercise is time-variant in healthy adults

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Left atrial phasic function interacts to support left ventricular filling during exercise in healthy athletes

Pulmonary hemodynamic and right ventricular responses to brief and prolonged exercise in middle-aged endurance athletes.

The pulmonary artery wedge pressure response to sustained exercise is time-variant in healthy adults