The main functions the right heart has to comply with are to accommodate the entire venous return and to transmit the blood into the pulmonary circulation for gas exchange [89, 90], thereby maintaining low right atrial (RA) and pulmonary pressures and optimizing varying amounts of venous return [15, 17, 83]. In order to do so, the right ventricle function has to integrate preload, afterload, contractility, pericardial constraint, interaction with the left ventricle, and cardiac rhythm [1, 3, 91].

The pressure difference between the pressure in the periphery (systemic filling pressure) and the right atrium (central venous pressure) determines the amount of venous return and ranges usually between 7 and 10 mmHg at which the RA-P is normally 0 mmHg [92]. In healthy persons, only a very low isovolumetric contraction pressure is needed to be generated by the RV [93, 94] in order to eject blood into the low-resistance, high-compliance and low-impedance pulmonary vessel system [95–97]. Thus, in healthy individuals with notable physiological LA filling pressures and pulmonary vascular resistance, a negligible RV contractile contribution is required to allocate adequate CO [17]: Simply the negative pleural pressures physiologically produced by normal breathing promote blood flow through the pulmonary circulation [97].

Indeed, the anatomical conditions of the right ventricle (thin-walled, crescent shaped in a cross sectional view, but triangular in a side view [98], and particularly the direct geometry of the RV) allow not only to adapt to large increases in right ventricular filling volumes due to high venous return [99, 100], but also, despite often dramatic varying amounts of venous return, to definitely maintain a more or less constant CO [101, 102]. This crescent shape with a concave free wall and a convex septum [99] means that the RV has a markedly lower volume to surface ratio in comparison to the left ventricle and thus a much higher compliance [103]. However, these anatomical features and physiological properties of both the RV (high compliance, increasing not declining wall stress during systole [17, 104]) and the pulmonary vascular tree (low-resistance, high-compliance and low-impedance), predispose the RV to significant chamber dilatation in case of acute after-loading [19, 103, 105–107], and imply that the right chamber can very poorly (even worse than the LV [108])—see Fig. 4.1—adapt to acute increases in PA input impedance [16, 19, 20, 109]. As such, in case RV afterload acutely increases, the until then healthy RV is found to be unable to generate mean pulmonary artery pressures of more than 40 mmHg [110].

Acutely elevated pulmonary pressure is the most frequent cause of acute right heart failure [14, 27–29]. It is predominantly an increased pulmonary vascular resistance (PVR) which leads to PH in any setting [16]. PH generally results from increases in pulmonary vascular resistance, pulmonary blood flow, pulmonary venous pressure, or a combination of these features [6, 111, 112]. Vasoconstriction (e.g. hypoxic alveolar vasoconstriction via direct pressor effects or due to mediators), thrombosis, and vascular remodelling may all cause PH [113], and are generally associated with increases in PVR [3, 15, 27, 41, 60, 114–117]. An elevated PVR indicates functional and/or structural pulmonary vasculopathy [115, 118–121].

Elevated left heart filling pressures, a hallmark of (left-sided) heart failure [111, 122], are recognized to cause pulmonary venous hypertension (PvH) [123] irrespective of LV-EF [124]. This is attributed to a backward, downstream transmission of the elevated left-sided filling pressures, precipitating a rise in pulmonary venous pressure [6, 115, 118, 122]. An elevation of the pulmonary venous pressure directly elicits higher intrapulmonary vascular pressures, particularly of the PAP, and a decrease in pulmonary vascular compliance, hence stiffens the pulmonary artery(ies) [25, 98, 100]. Consecutively, RV afterload and RV systolic wall stress increase, potentially compromising RV function [25]. However, in early stages, PvH is not found to exhibit abnormal high pulmonary vascular resistance and thus does not cause pulmonary vasculopathy [96, 125].

As such, LHD: ↑ in LVEDP → ↑ LA-P → ↑ downstream pulmonary venous p → ↑ pulmonary p and ↓ pulmonary vascular compliance (respective PA stiffening) → ↑ PAP [14, 25, 98, 125].

Finally, high flow conditions may be associated with PH, but show a normal PVR [120, 126].

Accordingly, although in most circumstances enhancements of the pulmonary artery pressure, PAP, are related to an increase in PVR, an increase in pulmonary pressures, namely mean PAP, and thus PH is not inevitably coupled with an increase in PVR [25, 125]. PH simply stands for elevated pressures in the pulmonary circulation rather than explicitly indicating pulmonary vascular alterations which are reflected by an elevated PVR [112, 118, 121]. However, PH may lead to increased PVR and to decreased pulmonary artery compliance [127]. A reduction in vascular compliance means an increase in vascular stiffness, which will cause a rise in vascular load on the upstream ventricle [96, 128–130]. RV-afterload is determined by the dynamic interplay between (1) pulmonary vascular resistance, (2) pulmonary vessel compliance, and (3) wave reflections [127], where PVR reflects the resistive RV-load component, and vascular compliance the pulsatile one [7]). Hence, PA stiffening also increases RV work load [127].

If PH is accompanied by a pathologic increase in PVR, adverse prognostic implications apply [131, 132].²

Anyhow, pathologically elevated pulmonary pressures, defined as a mean pulmonary arterial pressure ≥25 mmHg at rest, measured invasively by right heart catheterization [71, 126, 134], will impose an un-physiological pressure load (largely due to altered vascular properties) on the RV, provoking adaptive measures to face this burden potentially leading to right heart failure [14, 19, 20, 22, 23].

Physiologically, beat-to-beat variations in RV preload or afterload are addressed by adaption in right chamber dimension, applying Frank-Starling’s law of the heart: Abrupt, beat to-beat, increases in pre- or afterload are met with a mild rise in RV size, the so-called heterometric dimension adaptation (a diastolic effect), known as and described by Frank and Starling’s law of the heart [3, 135]. However, within a couple of minutes, starting already 20–30 s after the heterometric adaption applies, an increase in RV contractility, and as such a systolic adaptive effect, will firstly supplement but quickly completely replace the initial heterometric adjustment [3, 135]. This so-called homeometric reply, which does not require any pre-existing muscle or cellular hypertrophy [136], is referred to as “Anrep’s law of the heart [137]. It has been G von Anrep who demonstrated more than 100 years ago an intrinsically mediated increase in LV contractility in response to a raised LV afterload [137]. This reaction affecting the strength of contraction occurs independent of end-diastolic fibre length (the Frank–Starling–mechanism relies upon fibre stretch) or other extrinsic issues, like neuro-endocrine stimulation [138].

It has been challenged that the homeometric autoregulatory effect applies in vivo in the setting of a rapidly raised afterload since this mechanism has originally been demonstrated “only” in isolated muscle strips [139]. However, homeometric adaptation to afterload has been reported to apply in case the RV is exposed to pulmonary constriction if coronary perfusion is held constant [140]. Furthermore, some recent evidence even suggests that homeometric autoregulation may be the primary mechanism launched already for “initial” response and adaptation to brisk RV pressure load [141, 142].

However, physiologically, homeometric adaption replaces the heterometric adjustment after a few minutes as indicated by the chamber dimension, which returns to baseline after a few minutes, demonstrating the predominant role of homeometric (that is without chamber dilation), systolic function adaption in both acutely increased pre- and/or afterload [136].

Anyhow, up to 40% of RV systolic function, that means 2/3 of pressure and 80% of flow generation under healthy terms [143, 144], is derived from the LV systolic performance, largely from the septal oblique/helical orientated muscle fibre contraction, a feature referred to as systolic ventricular interdependence [14, 145, 146]. Of special note, these septal fibres, originating in the LV, reach up to the right ventricular outflow tract [147]. These bundles of muscle fibres functionally link RV and LV together and directly transmit contractile force generated by the LV to the RV [147, 148].

Oblique orientated myocardial muscle fibres are demonstrated to develop clearly more contractile power than transverse orientated ones [149], the latter typically found in the right ventricle [14]. RV dilatation, due to volume loading, increasing preload, or particularly due RV filling overload, as typically resulting from tricuspid regurgitation/insufficiency following RV dilatation, leads to a change in septal muscle fibre orientation, and the more transverse configuration implies loss of muscle strength [14]. This phenomenon is especially evident in LV systolic dysfunction where the naturally oblique orientated muscle fibres of the LV, and thus of the septum, take a gradually more and more transverse position, losing part of their power generation capacity, consecutively affecting RV systolic function as well [14]. On the other hand, an enhancement of the LV systolic function in the setting of a compromised RV function displays beneficial effects on RV performance [150].

Any rapid rise in pulmonary pressure (increase in PA input impedance) due to altered pulmonary vascular load, after-loading the right ventricle and/or a loss of RV contractility (altered myocardial properties, e.g. acute myocardial ischemia) causes an immediate increase in RV size, RV dilation, and concomitantly a rise in RV-end-diastolic filling volume (RVEDV) ensues [1, 3, 7, 16, 105–107]. However, RV adaption to PH is acknowledged to be decisively depend on the ventricle’s ability to adjust contractility in order to match the increased afterload the ventricle is facing in case of increased pulmonary vascular load [151, 152]. Accordingly, if the homeometric adaption is too short or even fails and cannot (fully) compensate for altered RV loading conditions, and/or if systolic RV (and/or LV) capabilities (contractile power) are suddenly lost (e.g. due to acute myocardial ischemia/infarction) [70, 74, 153, 154], heterometric measures persist or apply in addition, potentially able to meet (by applying the effects of the Frank-Starling-mechanism) the challenge imposed, although certainly at the cost of considerably increased RV dimensions (↑↑ RVEDV) [138, 155, 156]. This increase in RV size and filling is inevitably attended by increased right ventricular filling pressures (RVEDP) [23, 157–159].

If the RV dilates, it becomes a more cylindrical shape and thus the efficacy of the Frank-Starling-mechanism increases [141, 142]. However, under those circumstances, RV contractility is compromised (e.g. septal muscle fibre orientation, RV free wall performance) [14, 17, 133, 160], RV-EF impaired [31, 84, 161, 162], and RV pump failure and even cardiogenic shock may promptly ensue [89] if the compensatory mechanisms (most notably the increase in RV contractility as the predominant and physiological adaptive feature and alternative to match and face the elevated pressure load [135, 151, 152]) are insufficient and afterload mismatch persists [7]. As such, RV afterload has to be acknowledged as the major determinant of RV systolic function, and RV failure is commonly the result of increased RV afterload [14]. RV systolic function is much more than LV performance literally and crucially dependent on afterload [19, 163] (see Fig. 4.1).

Tricuspid regurgitation following RV enlargement may compound the conditions [1, 7], although they may also disclose a path to reduce RV afterload by offering a less restrictive way for the blood stream [164–166]. Furthermore, diastolic ventricular interaction (DVI) applies compromising left ventricular filling and thereby worsens global cardiac function and systemic circulation even more [83, 167, 168]. In any way, ventricular interactions (the ventricles are even more directly intertwined in malady [101]) play an important and critical role in RV-F pathobiology by taking a crucial impact on left heart and subsequently systemic cardiovascular function [145]. DVI, mediated by the pericardium and the interventricular septum (IVS) [1–3]), restricts left ventricular filling due to a leftward shift of the IVS in the presence of elevated pericardial constraint [1, 167, 169], thereby changing LV geometry [1, 170] resulting in impaired LV-contractility [3, 83]. Furthermore, due to the enhanced pericardial constraint resulting from RV-dilation, LV distensibility decreases, consecutively (as well) impeding LV filling, ultimately diminishing LV-SV [1, 3]. Subsequently, the compromised LV contractility may display considerable deleterious effects on RV systolic performance, systolic ventricular interaction, as about 1/3 (20–40%) of systolic RV pressure generation and up to 80% of RV flow generation [143, 144] results from LV contraction [145, 146, 171].

It is exactly ventriculo-arterial coupling which specifically refers to the relationship between ventricular contractility and afterload, in this case between the right ventricle and the pulmonary vascular tree [7]. As such, assessment of RV-PA coupling is a physiologic approach to this interrelated system [172]. Disrupted RV-PA-coupling is considered to contribute to progressive RV-malfunction [17]. RV-PA-uncoupling ensues as RV contractility does not match afterload [107, 173, 174]. Altered coupling may affect the efficiency of power transmission and thus dilutes blood flow output from RV to and within the pulmonary vessels, diminishing LV preload [22]. Indeed, recent studies report a reduced RV-PA coupling efficiency in different forms of PH [151, 175, 176]. In experimental tachycardiomyopathy RV-PA-uncoupling has been observed related to lack of a sufficient adaptive increase in RV contractility [177]. In a sepsis model with endotoxic-induced elevated PVR, initial preservation of RV-PA-coupling could not be maintained as the incipiently adaption in contractility did not persist [178]. On the other hand, several studies demonstrated preserved RV-PA-coupling in patients and animals with acute hypoxia related pulmonary vascular constriction (displaying acute RV pressure load), when RV contractility increased, matching the pulmonary artery input impedance [173, 174, 179, 180]. Accordingly, adaption of RV systolic function to increased pulmonary vascular load, causing PH, is necessary to maintain proper RV-PA-coupling. Uncoupling occurs in case of inflammation, long-lasting PH and left heart failure resulting in deficient RV contractile adaption (systolic ventricular interaction) [3].

The results consistently confirm the crucial role of homeometric adaption (incremental contractility) in case the RV is faced with a rapid or substantially raised afterload [151, 152]. RV-PA uncoupling is related to the onset of RV-failure and can be seen as an early sign of maladaption [181]. Deterioration of RV-PA coupling is associated with increased RVEDV [135], while the absence of increased RVEDV in the presence of raised pulmonary pressure indicates sufficient coupling [135].

Both, brisk increases in RV afterload (e.g. a sudden rise in pulmonary pressures inducing PH, but substantial and/or prolonged enhancements in RV vascular loading conditions as well) and rapid and/or particularly considerable boosts in RV preload (e.g. quick volume loading) [7, 98] lead to a marked RV-dilation [1, 3, 7, 19, 23, 31, 106, 107] with increased right ventricular filling volumes (RVEDVs) [1, 3, 7, 19, 23, 31, 106, 107]. An increase in ventricular filling volume is in any case attended by a rise in filling pressure: “Acute increases in filling volumes yield higher filling pressures” [157]-a parallel upward shift of the PV-relation (see Chap. 1, Sect. 1.​10). Acute volume loading of the RV or in case the RV dilates due to (abruptly) augmented RV afterload, both changes are enhancing RVEDV, and will thereby exert stress on the acutely literally indispensable pericardium which consecutively results in increased pericardial pressure and a noticeable parallel upward shift of the PV-relation, indicating that a higher absolute RV filling pressure is necessary to achieve a given RV filling volume [182]. As such, the increase in afterload itself exerts some impact on the position (parallel and upward) of the PV-relation. Hence, changes in vascular loading conditions result in parallel shifts of the diastolic PV-relation [157, 183] indicating alterations in pericardial and filling pressures (see chapter 1, section 1.​10, extracardiac forces). Moreover, pericardial constraint will affect the thin-walled RV more than the LV, subsequently the increase in RVEDP is disproportionally higher than that in LVEDP [168, 184]. However, increasing pericardial constraint, as with increasing RV enlargement, results in less RV free wall stretch, limiting the effect of the Frank-Starling-mechanism [17].

Furthermore, the markedly enlarged RV size is accompanied by altered diastolic RV properties, shifting the RV diastolic pressure-volume-relation to a steeper proportion of the curve (leftward and upward shift) as changes in systolic load affect diastolic properties as well [17, 156, 185–189]. This denotes RV stiffening, and as such, PH stiffens the RV [190]. RV stiffness dilutes the RV free wall stretch, consecutively blunting the Frank-Starling-effect [17], increasing RVEDPs and central venous pressures [1, 83]. RV diastolic dysfunction and elevated RV filling pressures induce renal fluid retention (arginine vasopressin effect) [1]. Thus, several effects are contributing to the quite substantial increase in RVEDP when suddenly after loading the right ventricle.

The increase in RV-size has, due to the acutely literally nondistensible pericardium [191, 192], an impact on the LV [1, 2]:

Hence in summary, LV size will substantially decline (LVEDV ↓↓) while LVEDP will increase (LVEDP ↑↑)³ and LV systolic capabilities will be diminished, as depicted by the following causal chain.

Noteworthy, RV accommodates much better and quicker to changes in preload (e.g. volume load) compared to the very poor tolerance of sudden (and/or substantial and/or prolonged) increases in afterload (pressure load) [19, 20, 100, 200]. In contrast to pressure overload, the right ventricle tolerates primary volume overload conditions over a long period quite well as evidenced by the clinical courses of patients suffering from intracardiac shunts (e.g. Eisenmenger’s syndrome), and tricuspid or pulmonary regurgitation [15, 17]. This may be due to:

Insofar, even acute volume loading alone will not induce predominantly acute right heart failure in otherwise reasonably normal hemodynamic conditions. However, acute and rapid or extensive volume loading, in particular over a certain limit [198] is reported to potentially cause transient RV-dilation in special circumstances [199, 203]. Volume loading should always be referred to as “pre-loading” the ventricle: In this respect, pre-load may be defined as the combination of all factors contributing to passive end-diastolic ventricular wall stress [7]. RV preload is determined by volume and pressure prior to contraction. Respiratory alterations affect the RV filling and the pericardium constrains the thinner, low-pressure RV more than the high-pressure LV [98].

Aside the more specific hemodynamic factors and features, further issues are demonstrated to significantly influence and contribute to the pathobiology of acute right heart failure:

A markedly enhanced activation of the neuro-endocrine and the immunologic/inflammatory-endothelial cascades displays a variety of functional alterations, particularly endothelial dysfunction (ED): Adrenaline and noradrenaline, angiotensin II (the most bioactive representative of the renin-angiotensin-aldosteron-system), cytokines, endothelin-1 in the presence of an altered NO metabolism and availability (a constellation typically indicative for ED), and natriuretic peptides (with their potential to counterbalance to some degree the effects of the aforementioned agents), are released and secreted, offering compensatory input, and as such are involved in and contributing to the pathophysiology of acute RV-D/RV-F [1, 83, 91, 204–211]. The release and discharge of adrenergic substances with positive inotropic and chronotropic effects may facilitate the contractile efforts [106], however, net contractility may be acutely even reduced [107].

These compensatory mechanisms applied with their predominantly pulmonary and systemic vasoconstrictive properties improve pulmonary blood flow and may temporarily stabilize the pulmonary and systemic hemodynamics [212], but are gradually maladaptive [27, 213, 214]. However, the increase in RV size and pressures lead to increased wall tension and cardiomyocyte stretch [106], consecutively the coronary perfusion is affected and a higher oxygen demand and consumption is displayed, potentially leading to RV ischemia [107, 215], at least if no effective reduction of RV afterload can be achieved [216]. In case of acute pulmonary embolism, causally responsible for the abrupt rise in afterload, RV ischemia is demonstrated to be of pathophysiological significance in the acute phase [217, 218]. Elevated RVEDPs and considerably diminished blood pressure not matching the metabolic demands may cause RV ischemia and compromised RV contractility [219]. Nevertheless, study results are inconsistent in regard to what degree ischemia is responsible for and contributes to RV contractile malfunction [220–222]. Moreover, myocardial stunning (even in case of RV-AMI) rather than true cardiomyocyte loss is suggested to underlie progressive contractile impairment [195].

Furthermore, there is some evidence suggesting that “just” pressure overload itself may down-regulate RV contractility [22, 223, 224]. In the absence of ischemia, activation of intracellular paths affecting the contraction sequence and procedure [225, 226], activation of apoptosis [227, 228] or even disturbed NO-pathways due to endothelial dysfunction may be involved.

As RV contraction will be prolonged (since myocytes prolong under stress contraction time action potential duration [7]) in case of RV strain, blood is still ejected into the pulmonary vessel system while the left ventricle already resides in diastole, the interventricular septum shifts to the left side in the late systole [229, 230] restricting and reducing LV-space [106, 107, 216]. This desynchronization of both ventricles will aggravate RV malfunction [7]. Dys-synchrony is reported to arise early on during the adaptive process, intended to support systolic function of the RV, however, this implies that LV-filling is blunted already early in the course [2].

If the hemodynamic compromise cannot be stabilized, as both, the (supplementary) heterometric efforts and especially the RV contractile power (homeometric adaption) are together not able to generate the performance necessary to match the acute increase in PA-input impedance (and/or the exposure of the RV to acute afterload mismatch persists), acute RV failure applies and may rapidly end up catastrophic with a circulatory collapse [95, 96, 135]. The progressive RV-dilatation and the accompanying, considerably elevated (and further rising) right ventricular filling pressure, reflecting and indicating RV-dysfunction/failure [25], may induce a vicious cycle ending up in circulatory collapse [135]. Even a mild acute elevation in pulmonary pressure eliciting mild PH may cause a substantial drop in RV-SV [231, 232]. Blunted RV-SV and thus reduced LV preload delivery (due to diminished SV generated by the weak RV [169, 194, 233] and due to RV-PA-uncoupling [107], both effects may be referred as to series-effects [169, 194, 233]), the excessive LV compression (largely due to DVI [135]), and the LV diastolic dysfunction (and therefore impeded LV distensibility) [81, 234], result in a marked LV underfilling [2, 3, 83] and a considerably impaired LV systolic function [2, 3, 83, 197, 198, 235].The combination of LV underfilling and compromised LV systolic function may inevitably precipitate hypotension and systemic hypoperfusion (adapted from Zochios, [93]). This will result in even less contractile support for the RV, while hypotension potentially dilutes right and left coronary perfusion contributing to circulatory collapse [107, 216, 236]. However, as discussed above, other, non-ischemic issues may contribute to the now progressively deteriorating RV systolic properties [22, 223, 224, 226, 228]. Though, “RV failure begets RV failure” leading into a progressive downward spiral of worsening myocardial dysfunction and incipient shock [93].

Once systemic pressure, e.g. MAP, begins to fall, hemodynamic collapse will ensue rapidly. As depicted in Fig. 4.2, a work by Guyton [89], the hemodynamic range within the disastrous malady course develops may be very narrow. Patients, of course with symptoms and signs of RV-F, although appearing to be in a clinically reasonable and stable condition with acceptable BP, but with no obvious evidence of relevant hypoperfusion, and only mild to moderately elevated CVP, may decompensate immediately and unexpected: Compensatory mechanisms may be already exhausted, but this is not recognized as clinical and hemodynamic features are still tolerable. Furthermore, no additional features (such as ischemia), typically aggravating the malady, may be observable. Nevertheless, issues including non-ischemic related paths [225, 227, 228], stunning myocardium [195] or RV-pressure overload associated, the contractile forces down-regulating mechanisms [22, 223, 237], and, hopefully not, therapeutic measures such as very cautious volume application (assuming a still available preload reserve in order to ameliorate rather than to destabilize the situation) may be the trigger of the disaster by initiating MAP to fall. Insofar, circulatory collapse may insert abrupt and quite unexpected in otherwise hemodynamically stable appearing patients.

In case of a gradual increase in PAP and/or PVR as usual in LHD, the so-called homeometric contractility adapation to afterload according to Anrep’s law [137] may ensue [135]. The homeometric adaption and remodelling is characterized by an increase in ventricular systolic function (e.g. contractility) without chamber dilatation in order to meet the load the ventricle is facing [138]: The right ventricle adapts to the increased afterload by increasing its wall thickness and contractility [7]. Homeometric adaption is shown to be the predominant feature of RV to face and to adapt to increased afterload and to ensure preserved RV-PA-coupling [3, 135].

Indeed, in case of gradual increases of pulmonary pressures or due to mild/moderately but chronically increased pulmonary pressures, RV develops a hypertrophy and thus concomitantly adapts [96, 151]. The initially enlarged RV end-diastolic volume triggers the development of RV hypertrophy enhancing contractile capabilities and thus adapts to the new challenge, maintaining RV-SV by increased contractile force [216]. In animal models, hypertrophy is recognized already 96 h after the onset of increased afterload [238]. This is principally confirmed by studies in humans suffering from ARDS where already after 2 days of PH (ARDS and mechanical ventilation cause an increase in transpulmonary pressure which correlates with the magnitude of RV afterload [95]), a moderate thickness of the free RV wall could be demonstrated [31]. Hypertrophy will reduce wall tension (LaPlace), and the interventricular septum, initially bulging to the left (D-shaping), flattens [216]. Notably, although the RV elastance may rise two-to three-fold during the acute phase, no acute systolic RV dysfunction has been reported [141, 142]—accordingly the enhanced RV–elastance indicates true augmentation in contractility. Moreover, some degree of RV-dilation establishing heterometric, dimensional adaptation via Frank-Starling-mechanism will be implemented as well [2].

However, if the load rises further, becoming too high for a too long period, or if these compensatory mechanisms are insufficient to match the load imposed, RV-PA uncoupling associated with (further) increased RVEDV occurs [135, 138], a heterometric adaptive mechanism, indicating RV dysfunction [7], or even RV-failure [3, 135]. Severe inflammatory conditions (e.g. septicaemia), long-term increase in PVR or advanced heart failure are disorders predisposed for RV-PA uncoupling and RV-dysfunction [3, 135]. Furthermore, even the described remodelling may, after many years of compensation, progress to chamber dilatation, consecutive tricuspid insufficiency, and frank RV-failure [172]. It may be speculated that pressure overload downregulates RV contractility [22, 223, 224] and thus later in the course, heterometric compensation will become necessary due to decelerating contractility. This is in line with recent study results, showing that patients with long-standing volume overload conditions, although compensated and most often only marginally symptomatic over many years, nevertheless carry an increased risk for cardiac morbidity and mortality [239, 240]. Other precipitating factors discussed include ischemia, as RV hypertrophy potentially decreases RV subendocardial perfusion, while the arising RV-dilatation entails increased wall stress and thus a higher oxygen demand [96] and neurohormonal/inflammatory issues [241–245].

Acute and chronic RV failure, being attended by enhanced neurohormonal discharge and sodium and water retention, is thereby consecutively accompanied by elevated CVPs [1, 24] which may exert deleterious effects: Increased CVP impairs lung lymphatic drainage, leading to interstitial pulmonary fluid accumulation causing shortened lung compliance, impaired gas exchange, and promotes the development of pleural effusion [5, 246]. Renal venous pressure is subsequently increased and provokes cardiorenal syndrome [5, 247, 248]. Hepatic and intestinal congestion occurs facilitating cholestasis and ascites development [1, 5], impairs gut absorption and may allow for translocation of gut microbes into the blood stream [96].

Cardinal clinical manifestations of RHF are exercise limitation and fluid retention [7]. Exercise limitation is the earliest sign of RHF and is a strong predictor of survival [349–351]. Exercise limitation is related to a decrease in flow reserve during physical stress [352–354]. Further, a reduction in peripheral blood flow can increase lactate production, contributing to muscle fatigue. Supraventricular tachycardia may contribute as well [355]. Syncope is a less common symptom often indicating severe limitation in flow reserve. RV failure may further lead to chronic kidney disease and hyopnatremia [356]. Congestive hepathopathy is often observed in patients with RHF and PAH, cirrhosis is a late complication.

Hemodynamically, acute RV decompensation is characterized by enlarged RV size with enhanced end-diastolic filling volume attended by an increase in RVEDP (acute increases in filling volumes yielded higher filling pressures [157]), RV diastolic dysfunction [156, 185], and diminished and falling CO [185]. Some patients with severe and progressive RV-F may even expire normal pulmonary pressures due to marked reduction in CO [1].Thus, the interpretation of PAP has to consider CO and severity of heart failure.

Patients presenting with acute decompensations of chronic PH can often clinically be barely distinguished from those with acute RV-F attributed to acute PE, as clinical presentations are very similar [1].

As such, although there are a lack of specific clinical signs in acute right heart dysfunction or failure [357] but, nevertheless, the following features are suggestive of acute RHF and may be present [9]:

The clinical presentation is furthermore markedly influenced and determined by the underlying source precipitating RV-F and existing comorbidities [83, 144].

To conclude, acknowledged clinical cardinal signs of RV-F include [1]

BNP has a strong, positive correlation to PVR and RVEDP in patients suffering from primary pulmonary hypertension [360, 361]. BNP rises gradually with increasing severity of RV-D/RV-F [306, 362, 363]. However, the thresholds of when to diagnose RV-D (RV-F) are still in discussion and vary from between >50 pg/mL [364] and >100 pg/mL [365]. Furthermore, elevated BNP levels may be present in chronic RV-D and chronic PH [208, 361, 366].

Troponin I > 0.1 μg/L (pathologically elevated) was found only in severe RV-D caused by pulmonary embolism [364]. Its occurrence is associated with early mortality [367, 368]. In the case of pulmonary embolism, patients with a negative serum troponin and normal ECG are at the lowest risk [369].

Both, Troponin and BNP have excellent negative predictive value and tend to exclude a complicated hospital stay when negative on admission [370, 371].

However, as both cardiac markers are not specific for right ventricular issues at all, the interpretation of their results can only be done in the clinical context they occur [2].

ECG ST-elevation (>0.1 mV) in VR3 and/or VR4 in patients with inferior ST-elevation acute myocardial infarction is highly specific for RV-ischaemia due to a proximal RCA-lesion (sensitivity 83%, specificity 77%) [64, 74]. Involvement of the RV, as a complication of acute inferior myocardial infarction (ST-elevation in II, III, aVF [372]) is to be expected in approximately 50% [70].

Direct pressure and volume measurements can be made using a Swan-Ganz-conductance catheter [373]. Although right heart catheterisation has previously been the method of choice, echocardiography, due to favourable comparisons to the catheter results and as the less invasive method, is now widely used [374]. An echocardiographic assessment is essential in establishing the diagnosis of RV-D/RV-F [2, 31, 365, 375–378]. Vieillard-Baron [379] requires only the finding of RV-dilatation with a leftward shift of the septum in order to make a diagnosis of RV-D; however, there are many other echocardiographic features of RV-D/RV-F which can be used to confirm the diagnosis:

TAPSE shows a good inverse correlation to the pulmonary vascular resistance (TAPSE ~ 1/PVR) representing pulmonary hypertension in cases of elevated resistance [305]. TAPSE is afterload dependent and pathological values indicate an elevated RV-afterload [305]. It is an excellent measure of the systolic RV-function [387–389] as it has a direct correlation with RV-EF (TAPSE ~ RV-EF) [307, 309, 386, 388]. TAPSE is a highly sensitive and specific parameter of depressed RV-SV [390] as RV-SV indirectly correlates with PVR [391].

Additionally, a good correlation is established between the severity of the tricuspid regurgitation (TR) and TAPSE (TAPSE ~ 1/TR) [305]. A normal TAPSE value is >22 mm [305, 392, 393], while 15–19 mm excursion indicates a moderate depression of TAPSE [305] and when < 15 mm the outcome is very poor [305]. However, TAPSE < 17 mm indicates a RV-LV disproportion reflecting the series and interdependent (DVI) effects of the failing RV on the LV-filling [2, 170];

Features indicating possible de-compensation of RV-F are [15]:

Special clinical settings and their echocradiographic correlates [2]:

Invasive hemodynamic assessments (and monitoring) are recommended in case the diagnosis is unclear or in therapy-resistant patients [2].

At rest, CVP normally equals 0 mmHg [403], and the CVP/RA-P are only elevated in disease states [404, 405]. Elevated (>8–10 mmHg) right atrial pressure/CVP is highly suggestive for acute right heart failure in a typical clinical setting [93]. A CVP ≥ 10–12 mmHg has already to be considered high, and will exert considerable constraint on LV filling [273, 278]. Thus, RA-P/CVP pressures ≥9–10 mmHg are always pathological and indicate that fluid application is highly unlikely to be successful [406] and that DVI will relevantly impact left ventricular filling, RV and LV filling pressures and the overall hemodynamic situation [273, 278].

In acute myocardial infarction with involvement of the RV early reperfusion by primary PCI is essential [412–417]; read more about this issue in Chap. 3, cardiogenic shock.

RV-F is the most common cause of death within 30 days following PE [110, 421] and RV dys-function is known to cause an increased mortality [110, 422, 423].

50% of all patients with pulmonary embolism present as clinically stable, without hypotension or circulatory failure, although suffering from RV-D [110, 365, 424]. They are at high risk of haemodynamic instability or even death during the first days after admission [425, 426].

The Shock Index is a sensitive parameter which can easily be used in daily practice in order to assess the potential outcome of patients with pulmonary embolism [289].

Thus, patients with a positive (≥1) shock index should be treated by thrombolysis (Evidence level A, Class I) [427–431].

Although not all studies give convincing evidence about the predictive and prognostic value of RV dysfunction [422, 423], Kucher [424] established that RV dysfunction is an independent prognostic predictor by analysing the data of the famous ICOPER study [110]. Patients with a systoli blood pressure ≥90 mm Hg (and thus classified as being hemodynamically stable/with preserved BP) but with RV-dysfunction had almost double the risk of death (16.3%) in comparison to those without RV-dysfunction (9.4%) over the first 30 days. Thus, although initially haemodynamically stable, all patients with RV dysfunction are at a high risk of death [424]. These results are consistent with those reported by Figulla [256], who found a 5–8% mortality rate in patients with normal BP but with RV dysfunction, while the prognosis of all patients without RV dysfunction was excellent (mortality rate 0–1%). It should be noted that the level of blood pressure taken as normal (sBP of >90 mm Hg versus >120 mm Hg respectively) was different in both studies and that the blood pressure on admission has a substantial impact on the patient’s prognosis [422] (see Table 4.2).

Not all studies have concluded that thrombolytic therapy reduces the mortality significantly when administered to clinically stable patients with RV-D but preserved BP [422, 423]. Nevertheless, the haemodynamic situation clearly improved and stabilised immediately after the patients received thrombolytic agents [110, 423, 426, 432–434]. Furthermore, the first prospective study assessing the long term outcome after first-time ‘submassive’ pulmonary embolism in previously healthy patients treated by heparin and warfarin found 41% of the patients either with persistent or subsequently (weeks to months after PE) developed RV abnormalities or functional limitations [435]. The authors suggest that first-time pulmonary embolism is able to cause persistent right heart damage or to initiate a process which damages the RV over time. The main pathological mechanisms involved appear initially to be ischaemia of the RV subendocardium followed by an inflammatory response [303, 436, 437].

The results by Kucher [424], Figulla [422] and Woods [289] suggest that patients in shock and those with hypotension need thrombolytic treatment, but it would also seem more than wise—based on the current evidence—to consider patients with established proof of RV-dysfunction on an individual basis for thrombolysis as well.

More recent studies and trials still demonstrate roughly 7% hospital and 32% overall mortality in hemodynamically unstable patients with PE [438]. Even RV-D and elevated cardiac biomarkers are indicative for increased risk of in-hospital death and clinical deterioration [439]. All studies and metanalysis substantially support the application of thrombolytic therapy in hemodynamic unstable patients with massive PE (defined as hypotensive patients or patients presenting with syncope, cardiogenic shock, cardiac arrest, or respiratory failure due to acute PE [215, 420, 440]). On the contrary, hemodynamically stable patients with submassive PE (defined as patients with acute PE being normotensive but with signs of RV dysfunction [441]), there still is an ongoing controversial discussion whether a clinically significant benefit can be achieved by thrombolysis [440–442], even though those patients also suffer from an increased risk of early mortality and adverse outcome [441]: The largest study on systemic thrombolytic therapy in patients with submassive PE in fact revealed that thrombolysis in that condition is preventive for circulatory decompensations, but at the expense of an increased ratio of intracranial bleedings [440]. Marti et al. found in their metanalytic study a reduced overall mortality and PE recurrence rate, and further a reduction of PE associated death, if thrombolytic therapy was given to patients with acute PE. However, in hemodynamically stable patients the benefit was statistically insignificant. Moreover, thrombolysis in PE was in general associated with a considerable risk of major intracranial bleedings [420], and the mortality reduction found resulting from thrombolysis is basically offset by the risk of fatal, particularly intracranial bleedings in hemodynamically stable patients with submassive PE [420]. Thus in hemodynamically stable patients with submassive PE, initiation of thrombolysis has furthermore to be based on thoroughly individual evaluation.