Are you ready for part 3 of the cardiology case challenge? In this next stage, Dr. Sundeep Mishra discusses responses to the questions posted in the previous part and puts forth further questions for the case discussion. 

Type your answers in the boxes below the questions. Professor Sundeep Mishra will share comments as the case progresses. Stay tuned! 

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For part 1, click here.

For part 2, click here.

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For our comprehensive coverage and latest updates on COVID-19 click here.

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Discussion on questions asked in Stage 2

This time we received around 140 responses.

Question 1: Is any other investigation required?

None of the respondents advised any new investigation but 40% advised follow-up investigations to predict course and guide further treatment. The investigations advised were:

1. Repeat cardiac biomarkers for prognosticating and monitor response to therapy; Trop T & I and other cardiac bio-markers
2. Repeat electrolytes and kidney function tests to guide therapy
3. Repeat haemogram and blood count to guide therapy
4. BNP & NT PRO BNP for prognosticating and monitor response to therapy

The investigations that were carried out and their results are as follows:

Hb	9.5
TLC	12400
PLT	2.9 L
Na	135
K	4.9
Urea	34
Creatinine	0.8
BIL	0.6

 

• Troponin T level - 25 ng/mL
• CK-MB - 104 ng/mL
• BNP - 8420 ρg/ml

Echocardiography: Examination was essentially the same as before with no increase in LV size or pericardial effusion. There was no evidence of RA/RV dilatation.

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Question 2: Which drug provides the best ionotropic support in shock related to decompensated heart failure?

• Dopamine
• Dobutamine
• Adrenalin
• Nor-adrenalin
• Vasopressin

Answer: Dobutamine is the best option – More than half of the respondents suggested dobutamine as at least one of the therapies.

When the shock is due to ineffective cardiac pumping, an ionotropic agent which increases contractility (β1 receptors) would be more useful. Among the ionotropic agents dobutamine has a predominant activity against β1 receptors with minimal activity against α or β2 receptors and is therefore the agent of choice in this situation. The table below shows activity of various ionotropes against various receptors.

Table Action of vasopressor / ionotropic agents on various receptors

Agents	Receptors
Adrenalin	β1≥β2>α
Noradrenalin	α=β1>β2
Dopamine	DA Receptors → release of endogenous noradrenalin + with high dose→α>—β1>β2
Dobutamine	β1>>α & β2
Vasopressin	V1 receptors → ↓portal blood flow, portal systemic collateral blood flow & variceal pressure but ↑PVR ↓CO & CBF

Adrenalin – 10% respondents

Dobutamine has a relatively long onset of action and therefore with severe hypotension, in emergency situations, due to its quick onset of action adrenalin may be more useful (β1≥β2>α). However, adrenalin should be used with caution because it may worsen myocardial dysfunction and could lead to increase in arrhythmias. Here it was a chronic condition and not an emergency; therefore use of adrenalin was not mandated.

Nor-adrenalin – 10% of respondents

As can be seen in the table, nor-adrenalin has a significant action on α receptors (which may cause hypotension and further worsen hypotension) and therefore may not be useful at least as a sole agent. In myocarditis, the primary problem is lack of contractility and not vaso-constriction and therefore an agent active more on β1 receptors than other receptors is more useful like dobutamine or adrenalin in emergency situations.

Dopamine – 20% of respondents

As can be seen from the table, dopamine acts on dopaminergic receptors, by release of endogenous nor-adrenalin. Moreover, in high doses they act directly by stimulating α>—β1>β2 and thus are not appropriate as a sole agent.

Vasopressin – 0%

Vasopressin is actually contra-indicated in this case because it acts on vasopressin receptor which actually decreases cardiac output. Moreover, in heart failure there is already a compensatory increase in ADH (arginine vasopressin), so giving more vasopressin will only worsen the decompensation especially in view that it can aggravate hyponatremia (a common complication in heart failure).

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Question 3: How do you treat hyponatremia and hypokalemia related to heart failure?

• Sodium supplementation

  • Hypertonic saline

  • Oral salt

• Fluid restriction

• Potassium supplementation

• Vaptans – Tolvaptan

Treatment of hypotonic hyponatremia is the most common disorder in heart failure and challenges clinicians on many counts. Despite similar serum sodium concentrations, clinical manifestations can range from mild- to life-threatening. Some patients require active management, whereas others can recover without an aggressive intervention (which might lead to overcorrection of hyponatremia. As can be seen, balanced therapeutic approach is critically important. In a given case it depends on

• Cause of hyponatremia – Euvolumic or hypervolumic
• Severity of hyponatremia – Clinical sign symptoms are equally or even more important than lab values

In our case, it is a dilutional hyponatremia (and hypokaelia) of heart failure. Furthermore, it is of mild variety (unaccompanied by signs/symptoms) even as far as lab values are considered.

Fluid restriction – 40% of respondents

In dilutional hyponatremia, the most common cause in initial (untreated/poorly-treated) heart failure. In hyponatremia caused by water retention, sodium and potassium stores remain essentially unchanged but body water is increased. Thus, fluid restriction (up to, 800 ml/d) is the first step and must be prescribed in all patients, excluding those with already ongoing aquaresis. In hypervolemic hyponatremia, fluid restriction should be complemented by a loop diuretic, which promotes aquaresis by reducing the hypertonicity of the renal medulla.

Potassium supplementation – 55% of respondents

Potassium supplementation is the next step because 1 mEq of potassium administration can actually increase serum sodium by at least 1 mEq (because of interaction of sodium and potassium). As a matter of fact, even partial correction of potassium depletion can cause an excessive rise in serum sodium even without sodium administration. Depending on clinical circumstances, potassium can be administered orally, intravenously, or by both, however, one has to be careful with the administration of potassium because failure to consider the effect of potassium replacement on the level of serum sodium has caused the most dreaded complication of osmotic demyelination. In our case, there was only mild hyponatremia (130 mEq/L - while severe is <120 mEq/L) and mild hypokalemia (3 mEq/L ) and thus, we undertook only oral potassium supplementation, rather successfully.

Hypertonic saline – 10% of respondents

Hypertonic saline may be required in emergency situations where there is symptomatic hyponatremia with serum sodium <120 mEq/L. This manoeuvre can lead to urgent correction but it can also lead to over-correction leading to osmotic demyelination (another serious emergency). Moreover, it can worsen the heart failure. As such, this extreme measure should be strictly reserved for emergencies.

Osmotic demyelination is a most serious demyelinating disorder typically involving the central pons (central pontine myelinolysis), but often extending into extrapontine structures (extrapontine myelinolysis). The root cause of this complication is overcorrection of hyponatremia that has undergone substantial brain adaptation. Its clinical manifestations, including hyperreflexia, pseudobulbar palsy, quadriparesis, parkinsonism, locked-in syndrome, and even death, arise 1–7 days after overcorrection of hyponatremia.

Oral salt – 15% of respondents

Again oral salt is a more drastic measure reserved for more serious hyponatremia. In our case, it could be easily managed with oral postassium supplementation.

Vaptans – 25% of respondents

Vaptans are vasopressin (ADH) antagonists and the stringency of fluid restriction can be lessened with the use of these drugs which promote aquaresis. These drugs can be administered intravenously (conivaptan, for up to 4 hospital days) or orally (tolvaptan, treatment must be initiated in the hospital) in hypervolemic hyponatremia of mild to moderate severity but not in hypovolemic hyponatremia. Since the aquaretic response to these drugs is variable, close vigilance; closely monitoring serum sodium is necessary. The introduction of vaptans generated great expectations, yet concerns about safety and cost currently limit the utility of these promising drugs for long-term management of hyponatremia.

At present, in heart failure with SIADH, the best therapy appears to be fluid restriction combined with careful potassium supplementation, plentiful sodium intake and loop diuretics.

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Question 4: How do you provide the best ventilator support to a patient in shock?

• Oxygen inhalation through nasal prongs

• NIV - CPAP - BPAP

• Full mechanical support with PEEP

Supplemental oxygen therapy has been used in the management of hypoxemic (peripheral oxygen saturation <94% or partial arterial oxygen pressure <60 mmHg) patients with acute heart failure since more than a century ago. On the other hand, there could be detrimental effects of oxygen therapy and subsequent hyperoxia in patients with normal oxygen saturation levels perhaps related to increased production of reactive oxygen species (and the related oxidative stress) and by the reductions in coronary blood flow and myocardial oxygen consumption resulting from hyperoxia-induced vasoconstriction in the cerebral, coronary, and systemic vasculature.

Congestive cardiac failure can arise from conditions affecting the myocardium, including myocarditis. In here, pulmonary oedema is a common occurrence that arises from increased left atrial pressure and imbalance in the Starling forces across the alveolar-capillary interface.

Lung compliance decreases as a result of fluid flooding the alveoli and interstitium, and the additional fluid in the capillary membrane creates a barrier for gas exchange. The resulting ventilation/perfusion mismatch causes hypoxia; the development of stiff, non-compliant lungs leads to an increased work of breathing, ventilatory failure, and CO₂ retention. Severe cardiogenic shock may further compromise the level of consciousness and the ability of patients to maintain a patent airway.

Many patients of acute decompensated heart failure may therefore be benefitted with intubation and some type of assisted ventilation which may not only decrease work of breathing but also directly decease alveolar oedema (consequent on pulmonary oedema) by increasing intra-alveolar pressure. On the other hand, very aggressive ventilation (associated with invasive mechanical ventilation with positive end-expiratory pressure - PEEP) may be associated with a significant decrease in pre-load of both LV and RV, which may be a cause of concern in context of volume depleted patients (over-treated heart failure). Thus, proper ventilation strategy is one of the key pillars in the management of complicated heart failure patients.

Oxygen inhalation through nasal prongs – 20% of respondents

With pulse oximeter O₂ saturation (SpO₂) of 92% in our patient, some sort of ventilator strategy is indeed necessary. Oxygen inhalation through nasal prongs is the first strategy but in our patient B/L basal crepts are also present suggesting of early pulmonary oedema; therefore some sort of breathing support will also be necessary/ideal.

Non-invasive ventilation (NIV) - 55% of respondents

When ventilation is delivered via a tight-fitting face mask or hood avoiding/eliminating the need of an endotracheal airway, it is termed NIV. It achieves comparative physiological benefits to conventional mechanical ventilation by reducing the work of breathing and improving gas exchange.

NIV works by creating a positive airway pressure - the pressure outside the lungs being greater than the pressure inside of the lungs. This causes air to be forced into the lungs (down the pressure gradient), lessening the respiratory effort and reducing the work of breathing. It also helps to keep the chest and lungs expanded by increasing the functional residual capacity (the amount of air remaining in the lungs after expiration) after a normal (tidal) expiration; this is the air available in the alveoli available for gaseous exchange. There are 3 types of NIV- CPAP, BiPAP, and Negative-Pressure Ventilation (NPV).

1. CPAP is the most basic level of support and provides constant fixed positive pressure throughout inspiration and expiration, causing the airways to remain open and reduce the work of breathing. This results in a higher degree of inspired oxygen than other oxygen masks. As well as having an effect on respiratory function, it can also assist cardiac function where patients have a low cardiac output with pre-existing low blood pressure by decreasing the LV pre-load. This was the type of ventilation we offered to our patient in question.
2. BiPAP provides differing airway pressure depending on inspiration and expiration. The inspiratory positive airways pressure (iPAP) is higher than the expiratory positive airways pressure (ePAP). Therefore, ventilation is provided mainly by iPAP, whereas ePAP recruits under-ventilated or collapsed alveoli for gas exchange and allows for the removal of the exhaled gas. In the acute setting, this type of ventilation is more useful in type 2 respiratory failure (e.g. COPD exacerbation), with respiratory acidosis (pH <7.35) – not the case here.
3. Negative-Pressure Ventilation (NPV) provides ventilatory support using a device that encases the thoracic cage, such as the iron lung. Although not seen as much in today's society, they were popular in the first half of the twentieth century during the polio epidemic. They work by lowering the pressure surrounding the thorax, creating sub-atmospheric pressure which passively expands the chest wall to inflate the lungs. Exhalation occurs with passive recoil of the chest wall. Their use may still be indicated in chronic respiratory failure (not the case here).

Mechanical ventilation (MV) with PEEP - 25% of respondents

This is the most aggressive type of ventilation which reduces the work of breathing (and thus, cardiac load) and may also have beneficial effects like decreasing cardiac (LV & RV) afterload and so cardiac work. However, it decreases cardiac pre-load (and thus harmful in volume-depleted patients such as over-treated heart failure) and may also affect coronary perfusion. Apnoea, severely depressed consciousness level, respiratory arrest, and severe cardiogenic shock are compelling indications for endotracheal intubation and, therefore, invasive MV (not the case here).

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Question 5: Would thyroid replacement therapy help this patient?

45% of respondents

In patients with pre-existing heart failure, subclinical hypothyroidism (high TSH but normal T4) is common and likely a result of a less active T3 hormone available to the heart through blood plasma, which raises the TSH (one of the endocrine consequences of heart failure), called “low T3 syndrome.” In this case, treating with levothyroxine (synthetic T4) can result in further decrease in T3; relatively high thyroxine/T3 ratio in serum with relatively low liothyronine levels in blood, which could further exacerbate the T3-deficient state in patients with chronic heart failure. This overall picture is associated with a higher risk for all-cause mortality, cardiovascular death, and major adverse cardiac events. Thus, treatment with levo-thyroxine can harm rather than benefit.

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Question 6: Would treating anaemia help?

• Oral haematinics

• Erythropoietin or analogue

• IV iron therapy

• Blood (packed cell) transfusion

Anaemia is highly prevalent in heart failure (HF) and is associated with increased morbidity in adults and children. Iron deficiency anemia, in particular, has been implicated in the development of a secondary cardiomyopathy but other mechanisms are also operative;

1. Haemodilution
2. Elevated sympathetic tone
3. Impaired oxygen delivery and myocardial oxygen extraction
4. Renal dysfunction
5. Poor dietary intake of micronutrients essential for myocardial function

Before starting any treatment for anaemia in CHF, it is necessary to exclude and treat, if possible, any other causes of anaemia, such as active bleeding, haemolysis, vitamin B12 or folate deficiency, or even more chronic situations such as myelodysplastic syndromes and other malignancies.

Dilutional anaemia is highly prevalent in CHF patients and mere fluid restriction, potassium supplementation and use of loop diuretics may be sufficient in milder cases. In more severe cases of dilutional anaemia, arginine vasopressin antagonists like tolvaptan might be an attractive treatment option, by increasing aquaresis.

The evidence till date does not convincingly support a role for erythropoietin or its analogues (10% of respondents) for anaemia correction. On the other hand, iron treatment (35% of respondents) may help ameliorate symptoms over the short term in patients with symptomatic heart failure. The role of blood transfusions (25% of respondents) is reserved for cases with severe anaemia (<9 gm%). In our case, anaemia was at least in part related to dilution ± of nutritional origin and therefore only oral haematinics (15% of respondents) started at the moment.

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Question 7: Can we do anything more for our patient?

ICU monitoring - 10% of respondents advised it, but in our case already, not only ICU, but haemodynamic monitoring (PCWP, ABP, ABG etc) was being carried out.

IV steroids - 10% of respondents advised it, but it was already given in our case.

Aspirin to prevent DVT/PE as a consequence of IVIG therapy- One respondent suggested use of ASA in context of IVIG therapy in our patient. There are a few case reports and one study suggesting occurrence of DVT/PE as a consequence of IVIG therapy. However, in all these studies, patients are adults (and not a child as in our case). Moreover, these studies generally recommend suing heparins or other anticoagulants (and not aspirin).

Cardiac transplantation - 10% of respondents advised it. A good suggestion, but not of much value in acute setting and with paucity of donor hearts at least in acute scenarios.

Cardiac assist device – One respondent suggested it. A good idea again, which will help tide over the consequences but could not be undertaken because of high cost of these devices (VAD, IABP, ECMO).

IV Antibiotics – Although none of the respondents have suggested it, we had indeed started our patient on IV antibiotics. Since many bacteria can also cause myocarditis (Borrelia burgdorferi, Mycoplasma pneumonia, Methicillin-resistant Staphylococcus aureus, Corynebacterium diphtheria) broad-spectrum antibiotics were started. Moreover, there could be bacterial infections as a consequence of lowered immunity due to viral infection.

• Ceftriaxone 2 g/day IV
• Vancomycin 15-20 mg/kg/dose IV q8-12h (not to exceed 2 g/dose)

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Further clinical course

• Patient haemodynamics improved
• SAO2 became 100%
• ABG – no acidosis
• BP 100/78 mmHg
• Patient became comfortable
• NIV pressure support tapered off
• Planned for heart transplant - Work up started

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Further questions

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This is a special, real-life case challenge series. Send in your responses latest by October 31 (Saturday).

Stay tuned for the next part which will cover the third stage of the case and the expert's discussion of the answers to the questions posted above.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Sundeep Mishra is a Professor of Cardiology.