Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Exercise pulmonary hypertension by the mPAP/CO slope in primary mitral regurgitation.

AIMS: Exercise-induced pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure over cardiac output (mPAP/CO) slope >3 mmHg/L/min, has important diagnostic and prognostic implications. The aim of this study is to investigate the value of the mPAP/CO slope in patients with more than moderate primary mitral regurgitation (MR) with preserved ejection fraction and no or discordant symptoms. METHODS AND RESULTS: A total of 128 consecutive patients were evaluated with exercise echocardiography and cardiopulmonary testing. Clinical outcome was defined as the composite of mitral valve intervention, new-onset atrial fibrillation, cardiovascular hospitalization, and all-cause mortality. The mean age was 63 years, 61% were male, and the mean LVEF was 66 ± 6%. The mPAP/CO slope correlated with peak VO2 (r = -0.52, P < 0.001), while the peak systolic pulmonary artery pressure (sPAP) did not (r = -0.06, P = 0.584). Forty-six per cent (n = 59) had peak exercise sPAP ≥60 mmHg, and 37% (n = 47) had mPAP/CO slope >3 mmHg/L/min. Event-free survival was 55% at 1 year and 46% at 2 years, with reduced survival in patients with mPAP/CO slope >3 mmHg/L/min (hazard ratio, 4.9; 95% confidence interval, 2.9-8.2; P < 0.001). In 53 cases (41%), mPAP/CO slope and peak sPAP were discordant: patients with slope >3 mmHg/L/mmHg and sPAP <60 mmHg (n = 21) had worse outcome vs. peak sPAP ≥60 mmHg and normal slope (n = 32, log-rank P = 0.003). The mPAP/CO slope improved predictive models for outcome, incremental to resting and exercise sPAP, and peak VO2. CONCLUSION: Exercise PH defined by the mPAP/CO slope >3 mmHg/L/min is associated with decreased exercise capacity and a higher risk of adverse events in significant primary MR and no or discordant symptoms. The slope provides a greater prognostic value than single sPAP measures and peak VO2.

Association between implantation depth assessed by computed tomography and new-onset conduction disturbances after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is often associated with intraventricular conduction disturbances. We aimed to determine the association between implantation depth assessed by multidetector computed tomography (MDCT) and new-onset conduction abnormalities after TAVR. METHODS: Retrospective single-center study including patients consecutively submitted to TAVR, between August/2007 and October/2016, who underwent routine MDCT 3 months after the procedure. The endpoint of conduction disturbances included permanent pacemaker implantation and/or new-onset left bundle-branch block. Implantation depth was determined as the distance between the ventricular end of the prothesis and the native ring, at the level of the non-coronary cusp. RESULTS: 138 patients were included (female gender 52.2%, mean age 78.7 ± 6.9 years). The EuroSCORE II was 4.0 ± 3.9% and 57.2% were treated with self-expanding prosthesis. The endpoint of conduction abnormalities was found in 45.7% (n = 63). The implantation depth was greater in the group with conduction disturbances (7.7 vs 6.4 mm, p = 0.006). Chronic obstructive pulmonary disease, oversizing and implantation depth were independent predictors of conduction abnormalities. Implantation depth had an AUC of 0.64 (p = 0.004) for the prediction of conduction abnormalities and a cut-off value of 7.1 mm predicted the composed endpoint with a sensitivity and specificity of 65% and 70%, respectively. CONCLUSIONS: Implantation depth assessed by MDCT is associated with new-onset conduction disturbances after TAVR. In patients with conduction abnormalities, which do not qualify for the immediate implantation of pacemaker, the assessment of implantation depth by MDCT may be an additional marker of risk to aid decision-making.

Circulating Biomarkers of Collagen Metabolism and Prognosis of Heart Failure with Reduced or Mid-Range Ejection Fraction.

BACKGROUND: Change in the architecture and composition of cardiac extracellular matrix is a key element in adverse cardiac remodeling that occurs during heart failure. Most of the times, the result is the development of fibrosis, which has a huge impact on the pathophysiology and clinical outcomes of heart failure syndromes. Several molecules related to collagen metabolism detectable in the blood have been proposed as biomarkers of myocardial fibrosis. Despite concerns regarding the true ability of these biomarkers to reflect quantitative and qualitative changes in myocardial collagen, a growing body of evidence suggests that they may play a potential role in several aspects of heart failure management. METHODS: This review aimed to summarize published data regarding the role of circulating biomarkers of collagen metabolism in the assessment of prognosis in patients with heart failure with reduced or mid-range LVEF ventricular ejection fraction (LVEF < 40% or LVEF 40-49%, respectively). Medline electronic database was searched to identify relevant studies published through October 2016. RESULTS: Most evidence regarding the prognostic value of collagen biomarkers in HF with reduced or mid-range LVEF lies on data concerning PIIINP and several MMPs and TIMP-1. Several prospective studies found that higher levels of PIIINP, several MMPs and TIMP-1 are associated with higher rates of mortality and/or HF hospital admissions in HF patients with LVEF < 50%. CONCLUSION: Circulating collagen biomarkers have been shown to play a role in prognostic stratification in heart failure patients with reduced or mid-range ejection fraction.