Critical Care Management of Decompensated Right Heart Failure in Pulmonary Arterial Hypertension Patients – An Ongoing Approach

By clinical perspective, RHF is a complex syndrome with signs and symptoms’ resulting from impaired RV structure or function and both appears to be common in severely ill patients [3].

Systolic RHF and diastolic RHF may present as isolated systolic or isolated diastolic RHF, however combined forms frequently require patient’s admission and treatment to the ICU. Tissue perfusion and oxygenation detriment is consequential to left ventricular underfilling and low cardiac output in systolic RHF. In diastolic RHF altered tissue perfusion and oxygenation as well, is the consequence of elevated systemic venous pressure [59]. Detailed pathophysiology mechanisms of right ventricular failure, ventricular interdependence, shifting of interventricular septum, pericardial mechanical involvement in RVF are detailed discussed elsewhere [5,60,61] (figure 1).

Fig. 1

Facing with a PAH patient with clinical signs of acute decompensated RHF failure including signs of low CO, congestion in the setting of RV failure reworking to pressure or volume overload, impaired venous return should be detected [62].

The greatest importance to the ICU monitoring of PAH and severe right-sided heart failure patients are clinical signs, cardiac and organ’s functions [16] (figure 2).

Fig. 2

Monitoring clinical signs is the first step in PAH patients admitted in ICU. WHO functional class improvement, maintaining sinus rhythm, reducing tachycardia, a negative fluid balance, decrease of jugular venous pressure, preserving a SBP over 90 mmHg with a MAP>70 mmHg, avoiding acute renal and hepatic injuries are mandatory. Urinary output measured by continuous catheterization must be >0.5mL/kg/hour. Commonly lab tests are depicted in figure 2. Serial checks of natriuretic peptides (BNP or/and NT-proBNP) levels should be completed.

Against the RV difficult anatomy, cardiac function evaluation and valve assessment by echocardiographic parameters is an essential key examination in monitoring the continuity of RV evolution. The right ventricle worsening, determining the ventricular dyssynchrony by time to peak strain is a good parameter to evaluate the interdependence of left and right ventricle [63].

In critically ill patients, serial quantitative RV function by tricuspid annular plane systolic excursion (TAPSE), S′ velocity of the tricuspid annulus, RV index of myocardial performance (RIPM) and/or fractional area change (FAC) assessment are supported by contemporary management of acute RVF [59]. Other parameters, such as right atrium area, inferior vena cava diameter, RV/LV ratio, and LV eccentricity index, pericardial effusion, and parameters of LV filling or advance use of the three-dimensional (3D) imaging studies, enhance the non-invasive evaluation of the RV dysfunction progression [64].

Management of PAH patients admitted in the ICU with acute RHF should target the reduction of pulmonary vascular resistance [52]. This could be achieved primary by identifying and prompt treatment of the triggering factors.

Invasive hemodynamic monitoring (arterial and central venous lines) is essential to guide therapy. The main goals are maintaining a normal blood pressure for each case, a CVP of 8–12 mm Hg and tailor drugs administration for a normal CO. Standard placement of a pulmonary artery catheter or a Swan-Ganz one to monitor PCWP, PVR, CO, and transpulmonary pressure gradient is attributable in complex patients [65]. An adequate titration of prostanoid therapy, inotropes, diuretics can be driven by the real-time data obtained, but these catheters are carrying-out the risk of arrhythmias [66]. Advanced hemodynamic monitoring can be performed using minimally/non-invasive systems such as pulse index continuous cardiac output device (PiC-CO), lithium dilution techniques (LiDCO) [67,68]. In special conditions (extended hemodynamic evaluation or severe PAH patients) right heart catheterization can be considered.

Common treatable triggering factors who determine ICU admission of PAH patients are represented by infection, arrhythmias, anaemia, pulmonary embolism, systemic hypotension, or specific medication withdrawal/noncompliance [16].

Infections (including sepsis, infective endocarditis, cerebral abscesses, confirmed HIV) are important negative prognostic factors for mortality in PAH patients admitted in the ICU. They are substantial evidence in favour of connections between gut pathology and PAH [69,70]. The presence of biofilms on indwelling medical devices is another important source of infection. When are diagnosed (isolation of microorganism or high clinical suspicion, radiologic findings, blood samples), prompted targeted treatment decision should be taken by a multidisciplinary team (including infection diseases advocacy). Removal the possibly infected line should be performed, but an alternative route (preferably a central line) must be commenced before (caution related to short half-time of prostacyclins).

With limited and various patients study population, the burden of arrhythmias in PAH mostly supraventricular (tachycardias, atrial fibrillation, atrial flutter, and atrioventricular nodal re-entry tachycardia), and ventricular arrythmias is less clear [71]. Supraventricular arrythmias (SVA), with a cumulative incidence ranging from 13.2% to 25.1%, are linked to a marked clinical deterioration, and considered to be a negative prognostic marker of evolution to the end-stage [72, 73, 74, 75]. The onset of SVA is associated with right ventricle failure and death [76]. The maintenance or restoring sinus rhythm should be pursued; rhythm control is another option. Among medications used in the treatment of arrythmias, the first choice is Amiodarone; other drugs (Digoxin, Sotalol, Dronedaron, beta-blockers, CCBs) are less studied and they should be used in well-definite scenarios, carrying-out a high-risk in patients with severe RV dysfunction. Alternative procedures - direct electric cardioversion (DCCV) or electrophysiologic therapies (ablations, AAD’s, overdrive pacing) must be also individualized and performed in specialized centers [77]. DCCV requires anaesthetic support, carries out a significant risk, and should be ordered before irreversible haemodynamic changes occur. There are no clear indications for prophylactic implantation of ICD in PAH patients [78]. Anticoagulation should be initiated in all patients accordingly to individual patterns. The CHA2DS2-VASc score is not validated in PAH.

Anaemia can precipitate acute RHF in PAH patients, encompasses different etiologies and, therefore, should be carefully corrected [79]. The real incidence of iron-deficiency anemia is not well-known in PAH subgroups, but represents a common comorbidity in HF. Iron replacement using intravenous ferric carboxymaltose may be used in acute episodes of HF in PAH patients, reducing hospitalization but the effect on 1-year mortality is still in debate [80,81].

Haemoptysis represent a potentially cause of acute anemia in acute RHF PAH patients. Depending on etiology (including previous anticoagulation), severity, and source of bleeding, it can negative impact the patients management. Severity of haemoptysis can be closely related to the underlying mechanisms: pulmonary embolism, and/or the sequence of elevated PAP, development of functional microvascular networks and association of changes in the structural and functional bronchial arteries.

Bleedings related to anticoagulants address their withholding, the use of traditional reversal agents including prothrombin concentrate in case of vitamin K antagonists or novel reversal agents for DOACs (Idarucizumab, Adexanet alfa) [82,83]. Particular cases of bleedings in PAH-Eisenmenger syndrome-related should be prudentially treated with tranexamic acid. In abundant haemoptysis, tranexamic acid represents an option for rapid resolution of bleeding in case of multiple bronchial artery embolization is unavailable [84,85]. Specific PAH cases with major haemoptysis should grant the use of desmopressin [86].

In PAH patients with acute RVF related to an of acute pulmonary embolism episode, treatment should be initiated accordingly to current guidelines, but the effect of thrombolysis can be unpredictable [59,87].

Oxygen inhalations reduce PVR hypoxia-related, mPAP and improve cardiac output [88]. As is stated by Price et al, inadequate oxygenation can exacerbate pulmonary vasoconstriction via hypoxia, hypercapnia and acidosis [89]. Oxygen saturations (SaO₂) should be kept above 90% in rest, and when sleeping [79]. As a general warning mechanical ventilation possess a high-risk during induction and ventilation itself with potential negative haemodynamic effect (systemic vasodilation, increasing PVR); thus auto or low (≤10 cmH₂O) PEEP, a 6 mL/kg/min tidal volume if tolerated, a plateau pressure lower than 30 cmH₂O are recommended in PAH patients who experienced ARDS [60,90]. For patients with refractory hypoxemia, alternative support methods such as high-flow nasal oxygen cannula, continuous positive airways pressure (CPAP) and non-invasive ventilation can be used [91].

Fluid management is challenging in PAH patients with acute right heart failure. Usually PAH patients who experience an acute episode of decompensation are hypervolemic, but optimal filling point is variable [66]. Tailored dosage of loop diuretics (such as furosemide) in continuous infusion will determine volume depletion with reduction of RV preload, RV wall tension, augmentation of ventricular interdependence and LV diastolic compliance [76]. In selected patients a combination of loop diuretics and thiazides or ultrafiltration may be needed. Diuretic therapy supplementation by adding spironolactone in higher doses may be successful in acute decompensated episodes of HF in PAH patients as they are susceptible for secondary hyperaldosteronism [92,93].Management of hypervolemia by venovenous ultrafiltration is retained in particular cases of hypervolemic PAH patients [16,93].

Optimizing the cardiac output, myocardial contractility, and preserving systemic blood pressures with direct effect of coronary arteries perfusion pressure by increasing systemic vascular resistance are in close conjunction with above mentioned measures. The effects of commonly vasopressors and inotropes used in ICU admitted PAH patients are presented in table 3 (abbreviations are same as above). The use of these drugs should be well individualised.

Afterload pressure decreasing is important to enhance RV function via mechanisms targeting RV wall tension, rebalancing oxygen delivery-consumption, improving coronary perfusion, increasing RV stroke volume and LV filling [60]. All approved drugs for PAH treatment can be used (see table 2). Typically, due to rapid onset, shorter half-time, titratability, pronounced afterload reduction and reduction in mortality, continuous infusion of epoprostenol is the first option [94]. A special attention must be conferred to selexipag (a prostacyclin receptor agonist) which was not studied in acute care settings, but treatment should not be discontinued in already treated patients [95]. The rapid onset (15 minutes), peak effects (60 minutes) and a 4-6 hour duration of action of Sildenafil determine an increase of CO and decrease of mPAP and PVR; it can be used in ICUs orally and/ or intravenously with caution due to side-effects [10,96]. Initiation of up-front triple therapy with epoprostenol, ERA’s and PDE-5 is also suitable for critically ill PAH patients [97].

The usual dosage and duration of action of agents used to optimize preload, myocardial contractility and diminishing right ventricular afterload, including pulmonary vasodilator therapy are presented in table 4.

Small and moderate pericardial effusions should be managed conservatively. In cardiac tamponade, immediate pericardiocentesis or surgical drainage is confirmed by echocardiographic parameters assessed during one respiratory cycle, using pulse wave velocity (PWV) in both mitral inflow and hepatic venous flow [98].

In particular situations of non-responsive to acute therapies cases is crucial to include the right ventricular mechanical circulatory support. Mechanical support of RV failure (i.e. extracorporeal membrane oxygenation membrane ECMO veno/venous or veno/arterial, or pumpless membrane oxygenators PA-LA, right ventricular assist device-RVAD) can be proposed as a bridge to recovery in acute decompensated naïve PAH patients, in treatable causes of acute decompensation of RHF, or overpassing to lung transplantation [16,60]. Survival of PAH patients admitted in ICU assessed with veno/venous ECMO can be predicted by the SAVE score [99].