Right heart failure and pulmonary hypertension for some reason occupy such a dominant position among the heart failure SAQs in the CICM Fellowship exam that the time-poor trainee may be forgiven for completely neglecting the left chambers of the heart, as something unlikely to be examined. The prevalence of this disease state in the past papers is of course completely divorced from its prevalence in the community. Though it is seen in perhaps 18-21% of heart failure cases, it is the focus of approximately 80% of the CICM past paper SAQs on the topic of heart failure, and so, much like the focus on fat embolism and medical gas supply testing, likely represents a form of construct misalignment (i.e where the assessment is designed in a way which cannot possibly address the intended learning outcomes of the curriculum). It does, however, help that the topic of right heart failure is fascinating -in the bizarre backwards-world of the right-sided circulation, everything is different and counterintuitive. The assessment and management of these complicated patients certainly require a level of skill and sophistication which would be consistent with that of an Intensive Care Specialist, and so on that level, it makes sense to throw this around in the final exams.
Though previously right heart failure was treated equitably along with the left in the chapter on the management of severe heart failure, the fact that the second paper of 2018 had allocated two questions to this topic has prompted a separate entry to deal with this issue. It is clearly something being emphasised by the college, and the savvy candidate will be well-prepared for the inevitable appearance of these topics in the vivas. The written past paper questions on right heart failure have consisted of the following SAQs:
The definitive resource for this is probably a nice ICU-centric review of acute right heart failure by Ventetuolo et al (2014). Haddad et al (2008) has probably the best breakdown of the aetiologies associated with right heart failure. The European ESC/HSA guidelines (Gorter et al, 2018) are the most recent at the time of writing, and likely represent the best single resource to revise management strategies. The American equivalent (Konstam et al, 2018, for the AHA) contains essentially the same material.
There are several ways of classifying the causes of right heart failure. In the infinite timespan permitted by an open-book exam scenario, one may use the excellent system recommended in Haddad et al (2008), where the causes are organised elegantly by the physiological abnormalities they generate. However, when cornered by a CICM examiner in the dark alley of a viva examination, the Part II exam candidate may spontaneously revert to a more primitive state, and produce some sort of stereotyped medical-student-like list of differentials organised according to a memorised mnemonic. As the objective of the exercise is to produce a list of plausible differentials, either approach should technically meet with the same degree of success. As such, both versions are offered below. Some of the more exotic causes mentioned by Haddad et al (double-chambered right ventricle?) are presented as links to some explanatory article or other, but one should not feel compelled to explore these culdesacs in the course of their exam revision.
Intrinsic myocardial disease:
This was the topic of Question 2 from the second paper of 2015, where 20% of the total mark were attributed to four features of right heart failure. As a disease process typically associated with many concomitant problems and flow-on effects, it is hard to separate the clinical features of right heart from the clinical features of left heart failure or pulmonary hypertension (which often cause right heart failure). The situation is made more complex by a lack of any single definitive resource. Resorting to Talley & O'Connor, one finds a list (p. 62 of the 5th edition) which is reproduced here mainly because the source was so influential during the formative period of many of the examiners.
Symptoms: ankle, sacral or abdominal swelling, anorexia, nausea.
General signs: peripheral cyanosis, due to low cardiac output.
Arterial pulse: low volume, due to low cardiac output.
Jugular venous pulse: raised, due to the raised venous pressure (right heart preload); Kussmaul's sign, due to poor right ventricular compliance (e.g. right ventricular myocardial infarction); large v waves (functional tricuspid regurgitation secondary to valve ring dilatation).
Apex beat: right ventricular heave.
Auscultation: right ventricular S3; pansystolic murmur of functional tricuspid regurgitation (absence of a murmur does not exclude tricuspid regurgitation).
Abdomen: tender hepatomegaly, due to increased venous pressure transmitted via the hepatic veins; pulsatile liver (a useful sign), if tricuspid regurgitation is present.
Oedema, due to sodium and water retention plus raised venous pressure, may be manifested by pitting ankle and sacral oedema, ascites, or pleural effusions (small).
Signs of the underlying cause:
- left ventricular failure (severe chronic LVF causes raised pulmonary pressures resulting in secondary right ventricular failure);
- volume overload (atrial septal defect, primary tricuspid regurgitation);
- pressure overload (pulmonary stenosis, pulmonary hypertension);
- myocardial disease (right ventricular myocardial infarction, cardiomyopathy).
This list has the merit of being focused on the examination findings in the same order in which they are found during a routine cardiovascular examination, which favours application to the scenario of the CICM hot case. Another way of organising these might be according to their pathophysiological relationship, as below:
Armed with a stethoscope and the aboveslisted information, one might feel confident about being able to make an assessment of right heart failure clinically, but how reliable is that, really? For logistic reasons, the answer has been pushed under the next <h2>.
Diagnosis and assessment of right heart failure has been asked about in several past SAQs, of which the most notable is Question 5 from the second paper of 2018 where clinical examination was compared to echocardiography and the Swan-Ganz right heart catheter. The college answer was uncharacteristically comprehensive and was used as the skeleton for the tabulated answer presented below (i.e. little was added except the table structure).
|Modality and findings||Advantages||Disadvantages|
(for more detail, see above)
With regards to answering the question asked above, the diagnostic accuracy of clinical examination is surprisingly good, perhaps because the signs are fairly unequivocal (i.e. you're either boggy with pitting oedema, or you're not). Mant et al (2016) performed a chart review and found the following clinical features with high specificity for heart failure (not specifically right heart):
The problem, according to Gorter et al (2018), is in the subtle difference in terms between dysfunction and failure. These authors and others have insisted that, whereas right ventricular dysfunction required PA measurements and echo to quantify, the diagnosis of right heart failure is clinical, and requires signs and symptoms. "However, the sensitivity of all of these features was low, ranging from 11% (added heart sounds) to 53% (oedema)" Mant et al complained. How can you make a diagnosis of anything with nonspecific and insensitive clinical findings? Now, go to the ICU, where the ventilated patient is uncommunicative, cannot be repositioned and has a mediastinum full of surgical drains. One is left to conclude that physical examination as a means of assessing heart failure in the ICU has only one major merit, it being cheap (depending on how long it takes and who does the examining in terms of dollars per hour) and relatively non-invasive (unless digital rectal examination routinely concludes your cardiovascular assessment). In this echo-heavy era, the persistence of Fellowship-level questions about clinical cardiac examination likely represents the effect of an ageing faculty on curriculum design.
- Preload management:
- Acute failure: increase preload to CVP 8-12 mmHg
- Chronic failure: decrease preload to CVP 8-12 mmHg
- Titrate using PA catheter (CO measurements)
- Afterload management:
- Prevent pulmonary vasoconstriction:
- Keep PEEP 6-10 cm H2O
- Keep SpO2 >92%
- Keep PaCO2 35-45 mmHg
- Keep pH 7.35-7.45
- Avoid high dose noradrenaline
- But: keep systemic BP at least above pulmonary BP
- Increase pulmonary vasodilation:
- Nitric oxide
- IV or inhaled prostacycline
- Bosentan, ambrisentan
- Sildenafil, tadalafil
- Dobutamine, for where PA pressure is normal
- Milrinone, for where PA pressure is raised
- Levosimendan, for where you really need a cardiac output boost
When the pulmonary arterial pressure was previously normal, increase the preload. With the (for example, acutely infarcted) right ventricle acting essentially as a passive conduit, the right side of the circulation becomes Fontan-like, where the central venous pressure becomes a dominant driver of flow through the pulmonary circulation. With the pulmonary vasculature offering little resistance to the flow of blood, this may actually be a workable solution, even though the 2018 AHA guidelines describe the approach as "simplistic". They still recommend a CVP target of 8-12 mmHg as a sensible endpoint.
When there is chronic pulmonary hypertension, decrease the preload. The ventricle is already pressure-overloaded and this is likely to impact the LV by means of septal "systolic bounce" where LV diastolic filling is impaired. There is probably little merit in further volume loading. On one hand, the increase in pressure (say, from CVP 20 mmHg to CVP 25 mmHg) will be a trivial influence when the RVSP is in excess of 80mmHg. On the other, to further dilate an already massively overloaded dilated ventricle will displace the septum further towards the left and produce worsening left ventricular failure, both in terms of systemic blood pressure and pulmonary oedema. In short, usually such a patient requires preload reduction instead.
When there is chronic pulmonary hypertension, don't decrease the preload too much. The loss of normal RV compliance means a higher pressure is required to achieve the same diastolic filling. A higher CVP will be required to maintain the stroke volume of the chronically failing right ventricle. How low is low enough? Again, experts (Ventetuolo et al, 2014) offer 8-12mmHg as their endpoint without much evidence in support of this recommendation.
Options to reduce preload include diuretics, CRRT and venodilators such as GTN. The AHA statement recommends escalating diuretic doses aggressively. The RV has a flattened Starling curve, which means much volume must move before there is a substantial improvement in its performance. Moreover, the combination of poor cardiac output and renal venous congestion means the response to diuretics will likely be poor.
How hard to hit the diuretics, one might ask? A good example can be found in the protocol of the CARESS-HF trial (Bart et al, 2012). Those guys gave 80mg IV loading doses of frusemide and then started with an infusion which escalated the dose rate from 10mg/hour to 30mg/hour if the urine output was below 3L/day (125ml/hr), together with regular doses of the thiazide metolazone. In that specific trial, this strategy was not inferior to ultrafiltration by CRRT, which is good to know if you've convinced yourself not to dialyse somebody because of their extensive premorbid decrepitude.
In virtually every situation except acute RV infarction, one ends up dealing with a situation where pulmonary vascular resistance is contributing to the RV dysfunction. Ergo, to decrease the pulmonary vascular resistance is a salutary goal in the management of right heart failure. This strategy has two broad components: one is to protect the pulmonary circulation from any additional afterloadyness, and the other is to do something specific to actively decrease their resistance.
The experts recommend this as their first line option. It also has the appealing logic of correcting physiologically abnormal parameters. Common ICU problems which also happen to promote increased pulmonary vascular resistance include the following:
Let's say one is in charge of some junior staff who might legitimately ask for specific physiological parameters as therapeutic goals. What specific values might one target if one were to do this scientifically? There is not much evidence out there which might be specific to acutely decompensated right heart failure.
Keep PEEP under 6-10 cm H2O. Where did this number come from? Schmitt et al (2001) titrated PEEP in ARDS patients, with PEEPS ("S" is for Suter et al, 1975) and PEEPA (A is for Amato et al, 1995) being around 6 cm H2O and around 13 cm H2O respectively. RV stroke output was calculated by multiplying pulmonary artery velocity-time integral (PAVTI) by the cross-sectional area of the RV outflow tract. With the higher "Amato-level" PEEP, the cardiac index decreased from 3.0 to 2.7 on average, even though it was supposed to improve lung recruitment and prevent hypoxic vasoconstriction. Lower Suter-era PEEP was associated with better cardiac output parameters.
This applies to patients who are already ventilated. Obviously, for those who aren't, avoidance of intubation and NIV is all-important.
Keep SpO2 >92%. This parameter is suggested by experts; in the sense that it is repeated multiple times across several contemporary papers (Ventetuolo et al, 2014; Patil, 2018; Lahm et al, 2010). None of these authors gives a reference to support their choice; they merely say "adequate oxygenation is of utmost importance" and "we therefore aim for oxygen saturations of 92%". Of course it is impossible to guess what happens in the minds of cardiology professors who get invited to write such articles. The lower PaO2 threshold for hypoxic pulmonary vasoconstriction is about 83 mmHg (Sylvester et al, 2012) which corresponds to oxygen saturation of around 95%, and so one wonders why not aim for this value instead. At a SaO2 of 92% (PaO2 64 mmHg) pulmonary vasoconstriction would be about 20-30% of maximum. In case you're wondering, half-maximal pulmonary vasoconstriction occurs at 40 mmHg PaO2, and the maximum is achieved at a dismal 2mmHg PaO2.
Keep PaCO2 35-45 mmHg. That's probably good advice at just about any juncture, but in this specific case, it has implications for pulmonary haemodynamics. Carvalho et al (1997) observed what happens to ARDS patients over a period of hypercapnia (where the PaCO2 was "permitted" to rise up to 55-60 mmHg or so) and found that the PA pressure increased from 25 mmHg to around 33 mmHg on average, with the PVR increasing by almost 50%.
Keep pH 7.35-7.45. Though a broader range might be safe under most circumstances, normal pH seems to favour pulmonary haemodynamics. Most authors tend to quote a graph from the 2000-era edition of Nunn's Respiratory Physiology (which appears to be missing from later editions), demonstrating an increase in hypoxic pulmonary vasoconstrictor response with progressively lower pH. This graph is reproduced here with neither permission nor modification. It originates from an ancient study by Rudolph and Yuan (1966). The authors' subjects were newborn calves; they used lactic acid and THAM to buffer the pH carefully, making recordings of PA pressure and PVR. It turns out, a pH of 7.20 produces a massive increase in pulmonary vascular resistance, no matter how normoxic you might be (it essentially doubles). At a pH of 7.1 the PVR is increased to three times the normal value. This is, in fact, a substantial change, when compared to the effects of oxygenation or hypercapnia as they are described above. Clearly, these people are going to benefit from some sort of alkalinising therapy.
Avoid pulmonary vasopressors. Of these, the most important one to know about would be noradrenaline, as it is in routine use everywhere and probably represents the first go-to choice of the poorly supervised night shift registrar. Fortunately, even fairly large doses of noradrenaline tend to produce only modest changes in pulmonary vascular resistance. Bousvaros et al (1962) gave unhealthy volunteers (mitral stenosis, ASD, etc) noradrenaline at a rate of around 20-40 µcg/min (i.e. around 0.28-0.57 µcg/kg/min for a 70kg person, or a fairly substantial rate). They demonstrated some increase in pulmonary vascular resistance, though in the experiment they needed to give noradrenaline boluses to separate its influence on the pulmonary circulation from the pulmonary consequences of its systemic effects (in this way, pulmonary vasoconstriction was seen 20-30 seconds earlier than systemic hypertension). The effect was not particularly vigorous (PVR rose on average by about 50 dynes.sec.cm-5/m2). One may conclude that the use of noradrenaline in these people is reasonably safe unless you use truly insane doses (in which case, it is unsafe no matter what your right ventricle is doing).
At the same time, it is important to maintain satisfactory systemic blood pressure. If the RV contracts against a mean PA pressure of 70 mmHg, and mean systemic arterial pressure is 60 mmHg, then with each contraction the RV wall is under pressure which exceeds its perfusion pressure, and some ischaemic subendocardial damage will begin to occur. Vlahakes et al demonstrated this in anaesthetised dogs in 1981. As pulmonary pressure and RV end-diastolic pressure increased, the coronary blood flow failed to increased to catch up with demand, and RV failure ensued - only to be reversed when the dog's aortic blood pressure was increased with phenylephrine. On the basis of these findings, authors such as Ventetuolo et al (2014) recommend that "the first goal of vasopressor therapy is to restore systemic blood pressure to levels above RV systolic pressure".
What's the net effect? It's probably positive. The college examiners, generally viewed as the gold standard for any question where the goal of answering is a CICM fellowship, trend towards using noradrenaline in right heart failure. In their model answer to Question 27 from the second paper of 2018, they commented that "the overall impact is that noradrenaline has been shown be helpful in RV dysfunction". That probably refers to papers like Schreuder et al (1989), which compared noradrenaline to other agents (in that case, dopamine) and found it non-inferior, which is a somewhat lukewarm recommendation given that these days dopamine is virtually absent from routine practice in the developed world. Ventetuolo et al (2014)
In order to maintain some semblance of structure and order, drugs which are colloquially described as "inodilators" are not included in this section, because for the majority those are inotropes with the desirable side-effect of pulmonary vasodilation. As such, they will be described in greater detail in the contractility section below. Here, the discussion will focus on drugs which have a pure vasodilator mechanism.
Nitric oxide is an inhaled pulmonary vasodilator. It has conventionally been used to improve the V/Q matching in severe ARDS by selectively vasodilating pulmonary vessels in the well-aerated regions of the lung. It will also work in a non-ARDS lung, where it should vasodilate the entire pulmonary circulation, wherever it reaches the alveoli. Bhorade et al (1999), in a cohort of 26 patients with acute right heart failure, found that the PVR decreased by about 20% on average with nitric oxide. Or rather, they found that 10-80 ppm of nitric oxide was required to achieve a PVR decrease of 20% ( the dose of which was titrated according to PA catheter measurements, and they were actually using PVR as their target endpoint). In many of these patients, systemic haemodynamic actually improved so significantly as the result of this seemingly modest improvement that systemic vasopressor infusions could be weaned. As such, where NO is available, people should consider its use.
Prostacyclin is another pulmonary vasodilator, which is slightly cheaper (hundreds of dollars per day, as opposed to hundreds of dollars per hour) and with a slightly longer duration of action (still measured in seconds). It also ends up being used in ARDS much more frequently than in RHF and therefore is usually available as an inhaled formulation, though strictly speaking one might prefer to give it intravenously if pulmonary hypertension was one's major concern. Charl et al (2004) described it as "safe, effective, and affordable" in the title of their article, describing a population of post-operative cardiothoracic patients. They also gave it an inhaled agent (that's what was available) and within the limitations of this method found a mean decrease in mean PA pressure of around 8mmHg. The corresponding improvement in cardiac output was modest (CI went from 2.6 to 2.8) but the PVR in these patients improved by about 50%, from around 350 to around 250 dynes.sec.cm-5/m2).
Bosentan, ambrisentan, sildenafil, tadalafil, riociguat: these drugs, though occasionally useful in the management of chronic pulmonary hypertension, are virtually unknown in the world of ICU-level acute right heart failure.
It basically comes down to "The unit stocks drug X and drug Y. Of these, which is going to be the least toxic?"
Dobutamine is an option: Ferrario et al (1994) used it in acute right infarction and found that the cardiac index increased (from 1.5 to 1.9, hardly a lifesaving victory). That was 5 μg/kg/min. It also appears to slightly decrease pulmonary arterial pressure, likely as a consequence of improving forward flow through the left side of the circulation. Most of the improvements seen with dobutamine appear to be from contractility augmentation, and therefore it will be most beneficial in situations where the PA pressure is essentially normal.
Milrinone generally thought to be a better choice for right heart failure, as it has direct pulmonary vasodilator properties. Eichhorn et al (1987) compared it to dobutamine and found them to be essentially identical (0.5 μg/kg/ min milrinone vs. 5 μg/kg/min of dobutamine). Both caused the same increase in cardiac index (around 25%), which is probably the most important parameter here. The main difference between them was the change in pulmonary pressure - milrinone dropped it by about 7-8 mmHg on average. As such, milrinone would be a better choice for right heart failure where RV afterload is a major factor.
Levosimendan is a newer substance, and therefore not as extensively researched. It too is an "inodilator" and therefore probably shares all the advantages of milrinone.
It was discussed in the college answer to Question 27 from the second paper of 2018, where the college examiners for some reason referred to it as "levosimendin", with some loss of credibility. All they said about it in their answer was that it "can improve RV function in left heart disease", which implies that the main effect of this agent is to unload the venous side of the pulmonary circulation and that it has little intrinsic effect on RV contractility. That's probably not completely accurate, but the statement is otherwise true, and probably refers to the findings of a study by Parissis et al (2006) which looked at patients with severe biventricular failure and found some distinct improvements in echocardiographic and neurohormonal parameters after a dose of levosimendan. The authors were not specifically coussed on RV failure, and the argument can be made, that the patients all had RV failure due to severe LV failure, and that improving the latter will have salutary flow-on effects for the former.
As to the right ventricule on its own, Hansen et al (2018) lamented the lack of evidence when writing their review of the use of levosimendan in right heart failure and pulmonary hypertension. It is possible to point to the study by Kleber et al (2009), who found that it reduces PVR in patients with severe pulmonary hypertension. However, in this group the improvement - though statistically significant - was negligible. Their baseline PVR was almost 500 dynes.sec.cm-5/m2 on average, and levosimendan dropped it by about 12 dynes.sec.cm-5/m2, which an improvement so minor that it could be described as trivial. Mean PA pressures decreased by a greater value (~14 mmHg), possibly owing to its effects on the left side of the circulation. The main benefit was from the effect of levosimendan on cardiac output. It more than doubled, from 4.3 L/min to 8.8 L/min. Surely, with this improvement in cardiac output, you'd be able to drive diuresis and generally clean up the mess that results from decompensated right heart failure.
There's not a lot out there, in terms of information on this matter. All we have is fragmented literature like Skhiri et al (2010), who briefly mention that "maintenance of sinus rhythm and heart rate control is important in RHF" but offer neither references nor specific target parameters. When posed with such a dilemma, one can only say that individual responses to tachycardia and atrial fibrillation will surely vary substantially and that a pulmonary artery catheter will be your best guide as to how therapy should be titrated.