Cardiogenic shock (CS) is a critical, life-threatening condition characterized by the heart’s inability to supply sufficient blood flow to meet the body’s metabolic demands.1 This leads to a systemic hypoperfusion response and multiorgan dysfunction. The pathophysiology of CS involves a cycle of reduced cardiac output, systemic inflammatory responses, and cellular death, ultimately resulting in significant morbidity and mortality if not managed in a timely fashion.2,3
The etiology of CS is diverse, with acute MI (AMI) and chronic heart failure with reduced ejection fraction (HFrEF) being the most common.1 A range of less prevalent CS phenotypes exists, each with distinct pathophysiological mechanisms and therapeutic implications. Among these, CS in the setting of restrictive cardiomyopathy (RCM) is a more challenging condition that necessitates a nuanced understanding of restrictive cardiac physiology and tailored management strategies.
While understanding that there are gaps in our knowledge on specific etiological subtypes of cardiomyopathy-related CS, this review aims to explore the pathophysiology, diagnostic approach, and management of CS in patients with RCM.4 We will highlight the unique challenges posed by this condition, particularly in terms of therapeutic options, given the distinct myocardial stiffness and diastolic dysfunction that characterize RCM.
Restrictive Physiology
Restrictive physiology is a hemodynamic state whereby ventricular filling is impaired due to increased myocardial stiffness, leading to elevated diastolic filling pressures that rise precipitously with only small increases in volume.
On echocardiography, restrictive physiology is often identified by a pattern of rapid early diastolic mitral inflow filling followed by a steep deceleration (<160 ms), as well as an increased ratio of early diastolic to atrial filling (=2), and impaired relaxation (decreased isovolumetric relaxation time) which all indicate abnormal ventricular compliance (Figure 1).
On invasive hemodynamic assessment, the hallmark of restrictive physiology is the disproportionate rise in intracardiac pressures with minimal increases in volume; atrial, wedge and ventricular end diastolic pressures are typically elevated and typically >20 mmHg in advanced disease. This pressure elevation is not related to extra-cardiac causes and presents with ventricular concordance on hemodynamic testing.5 This is to say that the findings from hemodynamic testing in patients with restrictive physiology are based on abnormalities of the myocardium and are not affected by respiratory changes. The stiff ventricle is unable to accept the contribution from atrial contraction and thus the x descent is blunted but a prominent y descent is evident due to high atrial pressures with rapid, short-lived filling of the ventricles (Figure 1).6
Restrictive physiology can arise in several conditions, including end-stage heart failure of various etiologies and even in cases of dilated cardiomyopathy, but is especially prominent in patients with RCM.
Restrictive Cardiomyopathy
RCM represents a distinct subset of cardiomyopathies characterized by increased myocardial stiffness and impaired diastolic function (Figure 2).7 RCM is usually non-dilated and features rigid ventricular walls, which limit diastolic expansion and lead to elevated filling pressures.6 While systolic function may remain relatively preserved, diastolic dysfunction is severe, resulting in symptoms of heart failure with preserved ejection fraction (HFpEF). Hypertrophic cardiomyopathy is usually identified as a separate entity, however, for the purpose of this review, we will include it in our discussion as a subset of restrictive cardiomyopathies.
Common etiologies of RCM include infiltrative diseases such as amyloidosis, sarcoidosis, and hemochromatosis, as well as idiopathic forms of the disease. Radiation therapy that affects the myocardium with distinct stiffening and reduced compliance is also part of the spectrum of restrictive cardiomyopathies, although it does not encompass the same pathophysiology. As such, this spectrum of disease creates another level of pathophysiological difference. This can best be highlighted by the example in Figure 3 of the two ends of the spectrum of RCM: advanced cardiac amyloidosis and radiation therapy-associated cardiomyopathy.
This dual physiology imposes a challenge when differentiating between the levels of restriction due to LV cavity confinement versus extensive myocardial rigidity and reduced inotropy with relatively preserved LV cavity volumes.
Cardiogenic Shock in Restrictive Cardiomyopathy
Pathogenesis and Progression
CS is defined as a state of inadequate tissue perfusion secondary to impaired cardiac output. It is typically characterized by hypotension (systolic blood pressure <90 mmHg or the need for pharmacological or mechanical support to maintain adequate pressure) and signs of end-organ dysfunction, such as altered mental status, oliguria, metabolic acidosis, and cold, clammy extremities.8
The development of CS in RCM is usually associated with an exacerbation of diastolic dysfunction. Triggers for decompensation into shock include arrhythmias, such as AF or ventricular tachycardia, acute MI, or progressive heart failure.
While the spectrum of restrictive cardiomyopathy differs between the specific etiologies, CS in restrictive disease encompasses an interplay between insufficient cardiac output related to reduced lusitropy and reduced cavity size, as well as decompensated cardiac output from reduced inotropy (Figure 4). As such, in restrictive and hypertrophic cardiomyopathy with smaller cavities, contractility may remain normal when assessed by ejection fraction with otherwise poor volume reserve. Patients with very small cavities may not typically respond to shock treatments due to this poor volume reserve.9
On the other hand, in cases of RCM with normal end-diastolic volumes, such as the example of radiation therapy-associated cardiomyopathy, reduced inotropy and contractility is the main driver of reduced cardiac output and hemodynamic shock. This is driven by the fibrosis and apoptosis of cardiomyocytes reducing cardiac contractility.10
Diagnosis
The diagnosis of CS in RCM requires a swift yet comprehensive clinical and imaging evaluation.
The presentation resembles typical CS patients with other etiologies. They may exhibit hypotension (as previously discussed, although not necessarily) and tachycardia as a compensatory response. Patients may also have varied degrees of organ dysfunction, which may include altered mental state, oliguria or anuria, and cool extremities. Pulmonary congestion is often pronounced, manifesting as dyspnea, tachypnea, and hypoxia in certain situations, with severe pulmonary edema.11
Laboratory abnormalities also reflect tissue and organ hypoperfusion. Serum lactate is typically elevated (>2.0 mmol/l) and acute kidney injury is common. Hepatic congestion or shock liver may ensue with right ventricular failure or poor perfusion and presents with elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and hyperbilirubinemia.11 Coagulopathy, characterized by prolonged international normalized ratio (INR) and activated partial thromboplastin time (aPTT), may develop.
Echocardiography provides essential information about diastolic function, filling pressures, and ventricular wall stiffness in patients with RCM and CS. Doppler imaging can reveal restrictive filling patterns with reduced E/A ratio and shortened deceleration time, and tissue Doppler can quantify abnormalities in myocardial relaxation (Figure 1), as mentioned before. Moreover, signs of decreased flow with reduced left ventricular outflow tract velocity-time integral (LVOT VTI), arrythmia-related reduced filling, or reduced intracavitary volumes all help in differentiating the cause of CS and improve the understanding of its pathophysiology related to reduced inotropy versus reduced lusitropy and limited chamber volume.
Invasive hemodynamic monitoring, including right heart catheterization, is often necessary to assess filling pressures and cardiac output, particularly in critically ill patients. RCM patients in shock will typically have elevated right and left filling pressures >15 mmHg and usually >20 mmHg with elevated pulmonary pressures and low cardiac index (<2.2 l/min/m²). This assessment allows for tailored treatments in a timely fashion with allocation of hemodynamic directed diuresis, chronotropic or inotropic therapies.
Other imaging modalities such as cardiac MRI may be invaluable in many cases to assess for myocardial fibrosis and infiltration once the patient is stable, particularly in infiltrative cardiomyopathies and storage disease when other specific treatments may be available.12,13
Management of Restrictive Cardiomyopathy
The treatment of RCM focuses on alleviating symptoms and addressing the underlying etiology when possible. This includes volume optimization, arrhythmia management, and heart failure therapies in certain cases.
The approach to increased fluid volume in patients with RCM is similar to patients with heart failure in general. The difference remains in the expected persistent elevated filling pressures after diuresis due to the noncompliance of the ventricular myocardium. As such, an adjusted filling pressure goal is usually attained with diuresis although there is a narrow window that results in symptom improvement without decompensating renal failure or hypotension. Moreover, care must be taken to avoid excessive preload reduction, which could compromise cardiac output, although very limited data support this diuresis approach.
There are also insufficient data to support the use of conventional guideline-directed medical therapy and pharmacological heart failure therapies in the management of RCM patients in general. ß-blockers and calcium channel blockers are sometimes used to control heart rate, especially arrhythmias, and optimize diastolic filling, although their benefit is variable. This is because the cardiac output in RCM is dependent on heart rate due to the fixed stroke volume. Therefore, ß-blockers can worsen hemodynamic function if the patient’s heart rate is reduced to an intolerable normal range. AF and other atrial arrhythmias are usually poorly tolerated in patients with RCM due to the loss of the atrial contribution to ventricular filling. Arrhythmia control also helps improve diastolic filling in those patients; however, severely dilated atria reduce the ability to maintain sinus rhythm. Anticoagulation in patients with AF and RCM is often indicated to reduce the risk of thromboembolic events.
There is no specific therapy for idiopathic RCM; however, most treatments are directed at specific causes of RCM. Infiltrative forms of RCM, such as amyloidosis and sarcoidosis, may benefit from disease-specific therapies, including transthyretin (TTR) targeted therapies or chemotherapy in amyloid light-chain amyloidosis, or immunosuppression in sarcoidosis.
Management of Cardiogenic Shock in Restrictive Cardiomyopathy
The management of CS in RCM is particularly challenging due to the underlying diastolic dysfunction and limited ventricular compliance (Figure 4). However, understanding the specific pathophysiology within the spectrum of RCM helps adjust treatment strategies.
In most common forms of CS, initial stabilization involves the use of inotropic agents and vasopressors to support cardiac output and maintain adequate perfusion. However, this strategy may be more beneficial for reduced inotropy rather than restrictive disease involving a volume-limited ventricle. Moreover, the use of inotropes must be balanced against the risk of arrhythmias, such as hemochromatosis and sarcoidosis, which are more prevalent in patients with RCM and can exacerbate hemodynamic instability. This said, 40–50% of patients with RCM or hypertrophic cardiomyopathy (HCM) awaiting heart transplantation are on inotropes.14
In patients with RCM, mechanical support options must be chosen with care due to the anatomical constraints imposed by small ventricular cavities. Devices such as intra-aortic balloon pumps (IABP) are being used more often to stabilize patients, with inotropic therapy and arrhythmia induction being avoided in those cases.9,14,15 In cases of cardiac amyloidosis, the use of IABP has shown improvement in mean arterial pressure, cardiac index, and cardiac power index.9 They also improved right atrial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure. Interestingly, the greatest benefit in improved cardiac index was seen in patients with larger left ventricular end diastolic diameter.
Temporary transvalvular mechanical circulatory support, such as using a temporary micro-axial flow pump (Impella), may provide a bridge to transplantation in selected cases; however, more data are needed in their use in RCM patients.16 Durable left ventricular assist devices (LVADs) are not typically used in RCM due to the same anatomical constraints, but certain subgroups of patients with mixed ischemic/non-ischemic diseases, or ‘burnt-out’ HCM phenotypes and reduced LV ejection fraction may benefit from this therapy. Care must be taken in those patients with RCM or HCM with smaller cavities due to inferior survival; left ventricular end-diastolic diameter >4.6 cm is reported to have better outcomes in this subgroup of patients.17 This approach deviates from previous precautions against the use of LVAD treatments in this population of patients.
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may be indicated in patients with profound shock, though left ventricular unloading strategies are often required to prevent worsening pulmonary congestion. This may be challenging in patients with smaller ventricular cavities. However, this may be a preferred approach in patients with biventricular involvement. Patients with cardiac amyloidosis and CS who are eligible for heart transplantation may benefit from this strategy and some centers employ it as a standard practice as a bridge to transplantation.18 Although this strategy remains uncommon for patients who are eligible for a transplant, there has been a significant increase in ECMO use in RCM/HCM patients.14
The TandemHeart (TH) system employs transseptal cannulation of the left atrium to divert oxygenated blood into the femoral artery.19,20 This method may be preferred in certain cases of RCM because the anatomical approach avoids the ventricular chamber. Small, randomized trials comparing the TH system to IABP have demonstrated superior hemodynamic performance with the TH system, however there is no randomized trial for RCM cases.21
Heart transplantation remains the cure for many of the RCM etiologies when patients have persistent shock states or profound clinical deterioration from elevated filling pressures. Most recent data show improved survival outcomes for patients with HCM post transplantation.22 The outcomes of RCM are comparable to non-RCM patients undergoing transplantation.23 This differs based on etiology with RCM due to radiation or chemotherapy having worse outcomes than other etiologies of RCM at 5 years.23 Improvements to cardiac TTR amyloidosis treatments and amyloid light-chain therapies have seen improved survival in 2014–2022 compared to previous years.23
Conclusion
CS in the setting of RCM represents a highly complex clinical challenge that requires a nuanced approach to diagnosis and management. Understanding the underlying pathophysiology of RCM and the factors that precipitate CS is essential for developing effective treatment strategies. Using advanced imaging, hemodynamic monitoring, targeted medical therapies, and mechanical circulatory support, clinicians can improve outcomes for these critically ill patients. Early recognition and tailored interventions remain pivotal to the optimization of survival and quality of life in this population.