Saturday, March 12, 2022

Review of anticoagulation in patients with Covid19 Key points:

 The following are key points to remember from this review on anticoagulation in patients with coronavirus disease 2019 (COVID-19):

  1. COVID-19 has led to unprecedented morbidity and mortality with >200 million cases and 4 million deaths worldwide. Apart from acute respiratory distress syndrome, COVID-19 is associated with thromboembolic disease.
  2. Viral entry through the endothelium may cause inflammation and vascular injury. Mononuclear cell activation can also trigger cytokine release and cytokine storm. Collectively, these lead to a prothrombotic state for patients with COVID-19. Other mechanisms may also contribute, including complement activation and anti-phospholipid antibodies.
  3. COVID-19 coagulopathy is categorized by laboratory abnormalities including increased levels of fibrinogen and D-dimer, mild prolongation of prothrombin time or activated partial thromboplastin time, and mild thrombocytopenia. Patients admitted with COVID-19 who have elevated D-dimer or troponin levels are associated with worse outcomes, including mortality.
  4. The incidence of venous thromboembolism in patients hospitalized with COVID-19 was 17% in a meta-analysis of 49 studies. The rate was higher in patients with critical illness (27.9%) as compared to those who were not critically ill (7.1%).
  5. Clinicians and researchers have explored the role of antithrombotic therapy to prevent COVID-19–associated thromboembolism. This includes use of standard prophylactic-dose anticoagulation, intermediate-dose anticoagulation, and therapeutic-dose anticoagulation given for prophylactic purposes.
  6. Several large observational studies have suggested that prophylactic-dose enoxaparin was associated with lower rates of intubation and death. However, the role of higher-dose prophylactic anticoagulation in preventing poor outcomes is not clear from observational studies.
  7. Two large trials have explored the use of anticoagulation outside of the hospital setting for patients with COVID-19. The MICHELLE trial compared rivaroxaban 10 mg daily for 35 days after hospital discharge with placebo and found a 67% relative risk reduction in their primary outcome without an increased risk of bleeding. Conversely, the ACTIV-4B study compared apixaban versus placebo in ambulatory patients with mild COVID-19 but was ended early due to a very low rate of thromboembolic events that did not meaningfully differ between treatment arms.
  8. Several trials have compared intermediate- or treatment-dose anticoagulation with standard prophylactic-dose anticoagulation in hospitalized patients with COVID-19. The multiplatform trial included 2,219 patients hospitalized without critical illness and found an increase in the number of organ support-free days with treatment-dose anticoagulation. In a concurrent trial of 1,098 critically ill patients in the multi-platform trial, treatment-dose anticoagulation did not increase the number of organ support-free days as compared to standard prophylaxis.
  9. In the HEP-COVID trial of 257 patients hospitalized with COVID-19 who required oxygen support and other risk factors, therapeutic-dose enoxaparin led to lower rates of thromboembolism and death as compared to standard-dose thromboprophylaxis. Similarly, in the RAPID trial of 465 patients with moderately ill COVID-19 and elevated D-dimer, therapeutic-dose heparin led to numerically (but not statistically) lower rates of death, intensive care unit (ICU) admission, and mechanical ventilation as compared to standard prophylactic-dose heparin.
  10. The authors are conducting a large-scale, prospective, multicenter, open-label randomized clinical trial of patients hospitalized with COVID-19 who will be randomized to receive prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary effectiveness outcome will be a composite of all-cause mortality, requirement for intensive care, systemic thromboembolism, or ischemic stroke within 30 days.

Geoffrey D Barnes MD., FACC

Review of renal compression in heart failure

 The following are key points to remember from this state-of-the-art review on renal compression in heart failure (HF):

Key points

  1. Previous studies have linked poor renal function in HF to both decreases in perfusion (due to low cardiac output) and increases in renal congestion (due to increases in central venous pressure). The latter is believed to play a significant role in worsening renal function (WRF) in HF.
  2. The authors hypothesize that three important mechanisms, alone or in combination, may contribute to renal congestion in HF: increased intracapsular, perirenal, and intra-abdominal pressures. These increases in pressure can lead to compression of the kidney and renal vasculature.
  3. Increased intracapsular pressure: As central venous pressures in HF increase, this leads to an increase in interstitial fluid in the renal parenchyma. Given that the kidneys are surrounded by a rigid capsule, volume expansion does not occur, which means increased interstitial fluid causes an increase in intracapsular pressure. This causes compression of renal veins, glomeruli, and tubules, which subsequently may lead to WRF.
  4. Increased perirenal pressure: Just outside of the renal capsule but within the renal fascia is the perirenal space, comprised mostly of adipose tissue. While not fully understood, increases in perirenal adipose tissue, as well as renal sinus fat within the kidney, may lead to renal vein compression and exacerbation of WRF in an already congested kidney.
  5. Increased intra-abdominal pressure: In patients with significant HF, increases in intra-abdominal pressure can be a result of many processes, which include development of ascites or retention of fluid in the splanchnic system. This leads to compression of renal vasculature and can contribute to WRF in HF. A similar effect can be seen in patients with significant obesity leading to increased intra-abdominal pressure.
  6. The authors suggest that renal decapsulation in HF patients may possibly lead to improved renal outcomes. Data from rat and piglet animal models suggest that decapsulation reduced renal tubular damage and ischemic acute kidney injury.
  7. The authors introduce the “renal tamponade” hypothesis to explain why significant WRF is present when central venous pressures are high in HF. Intra- and extra-renal compression of the kidney and renal vasculature through the above three mechanisms are major contributors.
  8. More research is needed to better define these mechanisms and to explore the possible benefit of renal decapsulation in managing WRF in HF.

Marty Tam MD., FACC,

6 March 2022


Review on LV Thrombus Following MI

 The following are key points to remember from this state-of-the-art review on left ventricular (LV) thrombus following myocardial infarction (MI):

  1. LV thrombus after acute MI (AMI) has declined significantly since the introduction of reperfusion therapy. The current estimate is that LV thrombus occurs in up to 6.3% of patients with ST-segment elevation MI (STEMI) and 19.2% of patients with anterior wall STEMI complicated by LV ejection fraction <50%.
  2. The imaging modality to detect LV thrombus greatly impacts the frequency of detection. Transthoracic echocardiogram (TTE) is inferior to cardiac magnetic resonance (CMR) imaging for detecting small, laminar LV mural thrombus. In fact, the sensitivity of TTE is only 29%, while the specificity is 98% as compared to CMR.
  3. CMR is the optimal imaging modality for diagnosis of LV thrombus. It maintains a sensitivity of 82-88% and specificity approaching 100% compared to surgical and/or pathological confirmation. Use of late gadolinium enhancement improves thrombus detection over cine CMR.
  4. Thromboembolic events caused by LV thrombi can be devastating. The risk of thromboembolism is most closely related to thrombus mobility and protrusion as described on imaging. The rate of thromboembolism varied between 3% in patients with consistently therapeutic anticoagulation and 19% in patients with poorly controlled anticoagulation.
  5. Most LV thrombi can be detected by imaging within 2 weeks of AMI. High-risk patients without LV thrombus on early imaging (e.g., within 48 hours after AMI) should be reimaged 2 weeks after the acute event.
  6. Virchow’s triad, which outlines the pathophysiology of thrombosis formation, applies to LV thrombus following AMI. Blood stasis from LV dysfunction and apical/anterior aneurysms is complicated by a hypercoagulable state from inflammation, elevated fibrinogen and neutrophils, platelet aggregation, and clotting cascade activation. This is further potentiated by tissue injury impacting the subendothelial tissue and exposing collagen.
  7. Therapies to prevent and treat LV thrombus following AMI also target Virchow’s triad. Guideline-directed medical therapy addresses issues of blood stasis, while anticoagulation addresses hypercoagulability and reperfusion therapy ± anti-inflammatory therapy addresses tissue injury.
  8. Prophylactic anticoagulation may be considered for patients with STEMI and anterior apical akinesis or dyskinesis. The 2013 American College of Cardiology/American Heart Association STEMI guidelines recommend use of a vitamin K antagonist (VKA) with a lower international normalized ratio (INR) target of 2.0-2.5. However, no prospective trial has examined the role of anticoagulation plus antiplatelet therapy in the modern percutaneous coronary intervention era.
  9. For patients who have been diagnosed with LV thrombus following AMI, studies have produced conflicting results regarding the safety and efficacy of VKA versus direct oral anticoagulants (DOACs). The authors recommend the use of VKA with goal INR 2-3. DOAC should be used if VKA cannot be tolerated.
  10. The authors recommend that repeat imaging be obtained after 3 months of therapy. If the LV thrombus has resolved, anticoagulation can be discontinued and dual antiplatelet therapy continued per management of AMI. If the LV thrombus is persistent, anticoagulation should continue with repeat imaging every 3 months. Once anticoagulation has been discontinued, repeat imaging 3 months later is advised.

Geoffrey D. Barnes, MD, MSc, FACC

10 March 2022