Pulmonary hypertension

In 2015, more than 800 papers were published in the field of pulmonary hypertension. A Clinical Year in Review article cannot possibly incorporate all this work and needs to be selective. The recently published European guidelines for the diagnosis and treatment of pulmonary hypertension contain an inclusive summary of all published clinical studies conducted until very recently. Here, we provide an overview of papers published after the finalisation of the guideline. In addition, we summarise recent advances in pulmonary vasculature science. The selection we made from the enormous amount of published work undoubtedly reflects our personal views and may not include all papers with a significant impact in the near or more distant future. The focus of this paper is on the diagnosis of pulmonary arterial hypertension, understanding the success of combination therapy on the right ventricle and scientific breakthroughs

The right treatment for the right ventricle

PURPOSE OF REVIEW: Right ventricular (RV) function is an important determinant of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although substantial progress has been made in understanding the development of RV failure in the last decennia, this has not yet resulted in the development of RV selective therapies. In this review, we will discuss the current status on the treatment of RV failure and potential novel therapeutic strategies that are currently being investigated in clinical trials. RECENT FINDINGS: Increased afterload results in elevated wall tension. Consequences of increased wall tension include autonomic disbalance, metabolic shift and inflammation, negatively affecting RV contractility. Compromised RV systolic function and low cardiac output activate renin-angiotensin aldosterone system, which leads to fluid retention and further increase in RV wall tension. This vicious circle can be interrupted by directly targeting the determinants of RV wall tension; preload and afterload by PAH-medications and diuretics, but is also possibly by restoring neurohormonal and metabolic disbalance, and inhibiting maladaptive inflammation. A variety of RV selective drugs are currently being studied in clinical trials. SUMMARY: Nowadays, afterload reduction is still the cornerstone in treatment of PAH. New treatments targeting important pathobiological determinants of RV failure directly are emerging

Vena cava backflow and right ventricular stiffness in pulmonary arterial hypertension

Vena cava backflow is a well-recognised clinical hallmark of right ventricular failure in pulmonary arterial hypertension (PAH). Backflow may result from tricuspid regurgitation during right ventricular systole or from impaired right ventricular diastolic filling during atrial contraction. Our aim was to quantify the forward and backward flow in the vena cava and to establish the main cause in PAH.In 62 PAH patients, cardiac magnetic resonance measurements provided volumetric flows (mL·s-1) in the superior and inferior vena cava; time integration of flow gave volume. The "backward fraction" was defined as the ratio of the backward and forward volumes in the vena cava, expressed as a percentage. Time of maximum vena cava backflow was expressed as a percentage of the cardiac cycle. Right ventricular volumes and aortic stroke volume were determined. Right heart catheterisation gave right ventricular and right atrial pressures. Right ventricular end-diastolic stiffness was determined with the single-beat method.The median (interquartile range) backward fraction was 12% (3-24%) and it was >20% in 21 patients. Maximum backflow occurred at near 90% of the cardiac cycle, coinciding with atrial contraction. The backward fraction was associated with maximal right atrial pressure (Spearman's r=0.77), right ventricular end-diastolic stiffness (r=0.65) and right ventricular end-diastolic pressure (r=0.77), and was negatively associated with stroke volume (r= -0.61) (all p<0.001).Significant backward flow in the vena cava was observed in a large group of PAH patients and occurred mostly during atrial contraction as a consequence of impaired right ventricular filling due to right ventricular diastolic stiffness. The backward flow due to tricuspid regurgitation was of significance in only a small minority of patients

When right ventricular pressure meets volume: The impact of arrival time of reflected waves on right ventricle load in pulmonary arterial hypertension

Abstract: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment-naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment-naïve PAH patients. In the treatment-naïve condition, 54% of patients had mid-systolic return of reflected waves (defined as 34–66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid-systolic return had more pronounced RV hypertrophy compared to those with late-systolic or diastolic return (RV mass/body surface area; mid-systolic return 54.6 ± 12.6 g m–2, late-systolic return 44.4 ± 10.1 g m–2, diastolic return 42.8 ± 13.1 g m–2). Out of 68 patients, 43 patients were further examined after initial treatment. At follow-up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL–1. Wave speed was attenuated from 13.3 to 9.1 m s–1, and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves. Key points: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. Larger volume at a given pressure causes larger RV wall tension. Early return of reflected waves adds RV pressure in early systole, when RV volume is relatively large. Thus, early return of reflected waves may increase RV wall tension. Wave reflection can provide a description of RV load. In PAH, reflected waves arrive back at variable times. In over half of PAH patients, the RV is exposed to mid-systolic return of reflected waves. Mid-systolic return of reflected waves is related to RV hypertrophy. PAH treatment acts favourably on the RV not only by reducing resistance, but also by delaying the return of reflected waves. Arrival timing of reflected waves is an important parameter for understanding the relationship between RV load and its function in PAH

Early return of reflected waves increases right ventricular wall stress in chronic thromboembolic pulmonary hypertension

BACKGROUND: Pulmonary vascular resistance (PVR) and compliance are comparable in proximal and distal chronic thromboembolic pulmonary hypertension (CTEPH). However, proximal CTEPH is associated with inferior right ventricular (RV) adaptation. Early wave reflection in proximal CTEPH may be responsible for altered RV function. The aims of the study are 1) investigate whether reflected pressure returns sooner in proximal than in distal CTEPH, and 2) elucidate whether timing of reflected pressure is related to RV dimensions, ejection fraction (RVEF), hypertrophy and wall stress. METHODS: Right heart catheterization and cardiac MRI were performed in 17 patients with proximal and 17 patients with distal CTEPH. In addition to determination of PVR, compliance and characteristic impedance, wave separation analysis was performed to determine the magnitude and timing of the peak reflected pressure (as % of systole). Findings were related to RV dimensions and time-resolved RV wall stress. RESULTS: Proximal CTEPH was characterized by higher RV volumes, mass and wall stress, and lower RVEF. While PVR, compliance and characteristic impedance were similar, proximal CTEPH was related to an earlier return of reflected pressure than distal CTEPH (proximal 53±8% vs. distal 63±15%, P<0.05). The magnitude of the reflected pressure waves did not differ. RV volumes, RVEF, RV mass and wall stress were all related to the timing of peak reflected pressure. CONCLUSIONS: Poor RV function in patients with proximal CTEPH is related to an early return of reflected pressure wave. PVR, compliance and characteristic impedance do not explain differences in RV function between proximal and distal CTEPH