A case of catastrophic antiphospholipid syndrome: first report with advanced cardiac imaging using MRI.

This present case pertains to a 48-year-old woman with a history of antiphospholipid syndrome, who presented with progressive fatigue, generalized weakness, and orthopnea acutely. She had a prior diagnosis of antiphospholipid syndrome with recurrent deep vein thromboses (DVTs) and repeated demonstration of lupus anticoagulants. She presented in cardiogenic shock with markedly elevated troponin and global myocardial dysfunction on echocardiography, and cardiac catheterization revealed minimal disease. Cardiac magnetic resonance imaging was performed, which revealed findings of perfusion defects and microvascular obstruction, consistent with the pathophysiology of catastrophic antiphospholipid syndrome (CAPS). Diagnosis was made based on supportive imaging, including head magnetic resonance imaging (MRI) revealing multifocal, acute strokes; microvascular thrombosis in the dermis; and subacute renal infarctions. The patient was anticoagulated with intravenous unfractionated heparin and received high-dose methylprednisolone, plasmapheresis, intravenous immunoglobulin, and one dose each of rituximab and cyclophosphamide. She convalesced with eventual myocardial recovery after a complicated course. The diagnosis of CAPS relies on the presence of (1) antiphospholipid antibodies and (2) involvement of multiple organs in a microangiopathic thrombotic process with a close temporal association. The myocardium is frequently affected, and heart failure, either as the presenting symptom or cause of death, is common. Despite echocardiographic evidence of myocardial dysfunction in such patients, MRIs of CAPS have not previously been reported. This case highlights the utility in assessing the involvement of the myocardium by the microangiopathic process with MRI. Because the diagnosis of CAPS requires involvement in multiple organ systems, cardiac MRI is likely an underused tool that not only reaffirms the pathophysiology of CAPS, but could also clue clinicians in to the possibility of a diffuse thrombotic process.

ADQI 7: the clinical management of the Cardio-Renal syndromes: work group statements from the 7th ADQI consensus conference.

Many patients with heart failure have underlying renal dysfunction, and similarly, patients with kidney failure are prone to cardiac failure. This has led to the concept of cardio-renal syndromes, which can be an acute or chronic cardio-renal syndrome, when cardiac failure causes deterioration in renal function, or acute and/or chronic Reno-Cardiac syndrome, when renal dysfunction leads to cardiac failure. Patients who develop these syndromes have increased risk of hospital admission and mortality. Although there are clinical guidelines for managing both heart failure and chronic kidney disease, there are no agreed guidelines for managing patients with cardio-renal and/or Reno-Cardiac syndromes, as these patients have typically been excluded from clinical trials. We have therefore reviewed the currently available published literature to outline a consensus of current best clinical practice for these patients.

Prevention of cardiac surgery-associated acute kidney injury.

Numerous strategies have been evaluated to prevent early CSA-AKI. Although correction of hemodynamic problems is paramount, there are no clinical studies that compare different hemodynamic management or monitoring strategies with regard to their effect on kidney function. Pharmacologic strategies including diuretics, different classes of vasodilators and drugs with anti-inflammatory effects such as N-acetyl-cysteine, do not appear to be effective. Most of the studies are underpowered and use physiological rather than clinical endpoints. Further trials are warranted with fenoldopam and nesiritide (rhBNP). Observational and underpowered randomized studies show beneficial renal effects of off-pump technique and avoidance of aortic manipulation. There is very limited evidence for preoperative fluid loading and preemptive RRT. Potentially nephrotoxic agents should be used with caution in patients at risk of CSA-AKI. Tranexamic acid or aminocaproic acid should be preferred over aprotinin. No pharmacologic intervention has been adequately tested in the prevention of late CSA-AKI. A singlecenter study, including a predominance of patients after cardiac surgery, showed a decrease of kidney injury with tight glycemic control.

Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

Dilated cardiomyopathy associated with simian AIDS in nonhuman primates.

BACKGROUND: Cardiomyopathy is being recognized with increasing frequency in patients with AIDS, yet the relationship between HIV infection and cardiac contractile dysfunction remains obscure. The purpose of the present study was to determine if infection with simian immunodeficiency virus (SIV) in nonhuman primates is associated with cardiac dysfunction and myocardial injury. METHODS AND RESULTS: Left ventricular size and function were determined by 2D echocardiography in 16 rhesus macaques before and at weekly intervals following infection with cloned pathogenic SIV(mac) 239 or the highly attenuated SIV(mac) 239 nef deletion mutant. A second group of 15 rhesus macaques chronically infected with pathogenic (n=6) or nonpathogenic (n=9) virus were studied at >2 years following infection. Cardiac tissues from 24 rhesus macaques chronically infected (>2 years) with pathogenic SIV were reviewed for evidence of cardiac pathology. Acute infection (<6 weeks) with either pathogenic or nonpathogenic SIV caused neither contractile dysfunction nor cardiac pathology. However, LV ejection fraction was significantly (P<0.05) depressed (43+/-7%) in rhesus macaques chronically infected with pathogenic SIV compared with rhesus macaques chronically infected with nonpathogenic SIV (61+/-3%). Furthermore, two thirds of rhesus macaques that succumbed to simian AIDS had myocardial pathology including lymphocytic myocarditis (n=9) and coronary arteriopathy (n=6), with complete vessel occlusion (n=4) and associated myocardial infarction and necrosis. CONCLUSIONS: This unique model is valuable in understanding the pathogenesis of cardiac injury associated with retroviral infection in a relevant nonhuman primate model of AIDS.

Combined angiotensin II receptor antagonism and angiotensin-converting enzyme inhibition further attenuates postinfarction left ventricular remodeling.

BACKGROUND: ACE inhibition (ACEI) attenuates post-myocardial infarction (MI) LV remodeling, but the effects of angiotensin II type 1 receptor (AT(1)) antagonism alone or in combination with ACEI are unclear. Accordingly, we investigated the effects of AT(1) antagonism, ACEI, and their combination in a well-characterized ovine postinfarction model. METHODS AND RESULTS: Beginning 2 days after transmural anteroapical MI, 62 sheep were treated with 1 of 5 treatment regimens: no therapy (control, n=12), standard-dose ACEI (sACEI; ramipril 10 mg/d, n=14), high-dose ACEI (hACEI; ramipril 20 mg/d, n=8), AT(1) blockade (losartan 50 mg/d, n=13), and combination therapy with sACEI+AT(1) blockade (CT; ramipril 10 mg/d+losartan 50 mg/d, n=15). MRI was performed before and 8 weeks after MI to quantify changes in LV end-diastolic and end-systolic volume indices (DeltaEDVI, DeltaESVI) and ejection fraction (DeltaEF). Change in regional percent intramyocardial circumferential shortening in noninfarcted segments adjacent to the infarct (Adj Delta%S) was measured by tagged MRI. CT resulted in the most marked blunting of LV remodeling: DeltaESVI (+1.0+/-0.4, +0.7+/-0.4, +0.6+/-0.3, +0.9+/-0.5, and +0.4+/-0.2* mL/kg); DeltaEDVI (+0.9+/-0.4, +0.7+/-0.5, +0.6+/-0.5, +0.9+/-0.5, and +0.4+/-0.3 mL/kg); DeltaEF (-24+/-7, -18+/-6, -14+/-7, -18+/-10, and -11+/-9* %); and Adj Delta%S (-8+/-4, -7+/-3, -5+/-3, -5+/-3, and -2+/-3* %) for Control, sACEI, hACEI, AT(1) blockade, and CT, respectively (*P<0.04 versus sACEI, AT(1) blockade, and control; P<0.05 versus control; P<0.002 versus AT(1) blockade and control). EDVI and ESVI at 8 weeks after MI were smallest with CT (P<0.02 versus all). CONCLUSIONS: Combination therapy with sACEI+AT(1) blockade shows promise in attenuating postinfarction LV remodeling but was not clearly superior to hACEI in the present study.

Contractile reserve and contrast uptake pattern by magnetic resonance imaging and functional recovery after reperfused myocardial infarction.

OBJECTIVES: We hypothesized that contrast-enhanced and dobutamine tagged magnetic resonance imaging (MRI) could investigate microvascular integrity and contractile reserve of reperfused myocardial infarction (MI) in one examination. BACKGROUND: In reperfused MI, microvascular integrity and contractile reserve are important determinants of functional recovery. METHODS: Twenty-three patients with a reperfused first MI were studied. On day 3+/-1 after MI, patients underwent tagged MRI at baseline and during infusion of 5 and 10 microg/kg/min of dobutamine followed by contrast-enhanced MRI (first pass and delayed imaging) after a bolus infusion of gadolinium-diethylenetriaminepenta-acetic acid. Tagged MRI was performed 9+/-1 weeks later (follow-up). Eighty-four transmural regions with hyperenhancement on delayed contrast-enhanced images were defined as COMB (first pass hypoenhancement) or HYPER (normal first pass signal enhancement). Percent circumferential segment shortening was measured within the subendocardium and subepicardum of each region of HYPER or COMB at baseline, peak dobutamine and follow-up. RESULTS: Shortening improved in COMB regions from 4+/-1% at baseline to 10+/-1% at peak dobutamine and 10+/-1% at follow-up, respectively (p<0.0003 vs. baseline for both). The HYPER regions likewise improved from 10+/-1% at baseline to 16+/-1% and 17+/-1%, respectively (p<0.0004 vs. baseline for both). Function within COMB regions was less than that of HYPER at baseline, peak dobutamine and follow-up (p<0.0003 for all). CONCLUSIONS: Dobutamine magnetic resonance tagging and contrast enhanced MRI are complementary in assessing functional recovery after reperfused MI. Regions of delayed contrast hyperenhancement demonstrate both contractile reserve and late functional recovery. However, if these regions demonstrate first pass contrast hypoenhancement, they are associated with greater myocardial damage.

Impaired posthypoxic relaxation in single cardiac myocytes: role of intracellular pH and inorganic phosphate.

OBJECTIVE: The aim was to examine the effects of alterations in intracellular pH and inorganic phosphate concentration (known to influence myofilament kinetics and to change rapidly during hypoxia) on cell contraction, relaxation, and the Ca2+ transient in normoxic and hypoxic myocytes. METHODS: Single adult rat ventricular myocytes were electrically stimulated (0.2 Hz) and cell length (photodiode array), intracellular Ca2+ (indo-1 fluorescence), or intracellular pH (SNARF-1 fluorescence) measured. Hypoxia was induced in a special open chamber in which a laminar layer of argon prevented the back diffusion of atmospheric oxygen. RESULTS: Electrically stimulated contraction was preserved during exposure to hypoxia. At reoxygenation 10 minutes later the time from the stimulus to the peak of contraction (TPK) increased by 30(SEM 9)% and the time from the peak of contraction to 50% recovery of cell length (RT50) increased by 59(13)% relative to prehypoxic values (n = 8). These changes were not accompanied by a change in the kinetics of the Ca2+ transient. pHi fell from a baseline of 7.33(0.04) to 7.25(0.03) during hypoxia and then overshot to 7.44(0.03) at reoxygenation (n = 5). Since an intracellular alkalosis can slow myofilament relaxation, proton extrusion routes were blocked to examine posthypoxic relaxation in the absence of an alkalosis. Despite inhibition of the pHi overshoot, posthypoxic relaxation remained impaired. Intracellular inorganic phosphate levels were manipulated in two protocols (2-deoxyglucose to "trap" phosphate and Tris(hydroxymethyl)-aminomethane to buffer phosphate) and both TPK and RT50 increased in normoxic cells. Having established that these two interventions, which would be expected to decrease intracellular inorganic phosphate, result in a slowing of relaxation, myocytes were first phosphate loaded (exposed to 5.0 mM phosphate) and then made hypoxic and reoxygenated after 10 min to blunt the expected fall in phosphate accompanying reoxygenation. This led to a reduction in the slowing of contraction and relaxation following reoxygenation [TPK increased by 7(5)% and RT50 by 17(9)%, n = 8; p < 0.05 v cells studied in control buffer]. CONCLUSIONS: Impaired posthypoxic relaxation is not the result of changes in pHi but is attenuated by phosphate loading of cells and may be due to a rapid decrease in intracellular phosphate accompanying the resynthesis of high energy phosphates at reoxygenation.

Combined angiotensin converting enzyme inhibition and angiotensin AT(1) receptor blockade up-regulates myocardial AT(2) receptors in remodeled myocardium post-infarction.

OBJECTIVES: In an ovine model of left ventricular (LV) remodeling after transmural anteroapical myocardial infarction (MI), we have previously demonstrated that the combination of angiotensin converting enzyme (ACE) inhibition and AT(1) receptor blockade is more effective at limiting LV remodeling than either therapy alone. We hypothesized that the beneficial effect of combined therapy is due in part to upregulation of AT(2) receptor levels. METHODS: Two days after transmural anteroapical MI by coronary ligation, 16 sheep were randomized to losartan (50 mg/day), ramipril (10 mg/day), ramipril+losartan (combined therapy), or no therapy. At 8 weeks after MI, radioligand receptor assay were deployed with homogenates from regional LV tissues. RESULTS: We found that AT receptors in normal sheep myocardium are predominantly of the AT(2) receptor subtype. Binding studies of remodeled myocardium 8 weeks later showed that the apparent maximum binding (B(max)) was increased from 23 to 48 fmol/mg protein only in animals with combined therapy. The AT(2)/AT(1) proportion was increased significantly in animals with combined therapy compared to infarcted controls (18.0 vs. 5.17). CONCLUSIONS: These results indicate that AT(2) receptor expression increased significantly during LV remodeling with combined therapy but not with either therapy alone. In combination with prior work demonstrating the effectiveness of combined therapy in limiting LV remodeling, this study is consistent with the hypothesis that AT(2) receptors play a cardioprotective role in LV remodeling after MI.

Quantification of the myocardial response to low-dose dobutamine using tissue Doppler echocardiographic measures of velocity and velocity gradient.

Low-dose dobutamine echocardiography has been clinically useful in myocardial viability studies, although routine visual assessment of wall motion is subjective. The objective was to quantify the incremental myocardial response to low-dose dobutamine infusion using a new semiautomated tissue Doppler (TD) analysis system and to compare these data with routine echocardiographic measures in the same subjects. Twelve subjects had TD and routine echocardiographic studies at baseline and during 10-minute stages of dobutamine infusion at 1, 2, 3, and 5 microg/kg/min. Color TD video data were converted to a digital velocity matrix (4.5 velocity data points/mm at 500 Hz) for analysis of mitral annular velocity, endocardial velocity, and velocity gradient at each stage. Posterior wall percent thickening and ejection fraction were calculated from the routine images. Mitral annular peak systolic velocity significantly increased with only 1 microg/kg/min of dobutamine from 69 +/- 9 to 77 +/- 7 mm/s (p <0.05 vs baseline), and further incremental increases occurred with each subsequent dose. Anteroseptal and posterior wall peak endocardial velocity increased with 2 microg/kg/min of dobutamine from 33 +/- 7 to 46 +/- 15 mm/s and 50 +/- 9 to 61 +/- 10 mm/s, respectively (p <0.01 vs baseline) and further increased with 5 microg/kg/min (p <0.0001 vs 3 microg/kg/min). Posterior wall peak systolic gradient also increased with 2 microg/kg/min of dobutamine from 3.1 +/- 0.6 to 5.4 +/- 1.6 s(-1) (p <0.05 vs baseline). Routine measures of percent wall thickening or ejection fraction did not detect increases until the 3 microg/kg/min dose. TD can detect subtle alterations in contractility induced by low-dose dobutamine and has the potential to quantify regional ventricular function objectively.

Release of lactate by the lung in acute lung injury.

UNLABELLED: The pathogenesis of hyperlactatemia during sepsis is poorly understood. We have previously described an increase in lactate concentration across the lung in the dog during early endotoxemia. Accordingly, we sought to determine if the lung releases lactate in humans and what relation this has with lung injury. METHODS: We measured lactate concentrations across the lung and lung injury scores (LIS) in two groups of patients. Group 1 consisted of nine patients with acute lung injury (LIS > or = 2.0) and elevated lactate concentrations (> 2.0 mmol/L). Group 2 contained 12 patients with no acute lung injury (LIS scores < or = 1.5), with or without increased lactate concentrations. Simultaneous measurements of plasma lactate and blood gases were obtained from indwelling arterial and pulmonary artery catheters. Measurements of cardiac output were also obtained. Lactate measurements were done using a lactate analyzer (YSI; Yellow Springs, Ohio). RESULTS: For each patient with acute lung injury and hyperlactatemia, an arterial-venous lactate gradient existed demonstrating release of lactate by the lung. This gradient persisted after correction for changes in hemoconcentration across the lung. The lactate gradient across the lung was 0.4 +/- 0.2 mmol/L for group 1 vs 0.05 +/- 0.1 mmol/L for group 2 (p = 0.001). This corresponded to a mean pulmonary lactate flux of 231.3 +/- 211.3 vs 5.0 +/- 37.2 mmol/h (p = 0.001). The lactate flux and the arterial-venous lactate difference correlated with LIS both for the entire sample and for the subgroup with hyperlactatemia (r = 0.69, p < 0.01). Pulmonary lactate flux was not related to arterial lactate levels (r = 0.25). CONCLUSION: In patients with acute lung injury and hyperlactatemia, the lung is a major source of lactate and lactate flux correlates with LIS. This lactate flux could explain some of the hyperlactatemia seen in sepsis.

Transesophageal echocardiographic identification of a malpositioned extracorporeal membrane oxygenation cannula.

Transesophageal echocardiography identified malposition of an extracorporeal membrane oxygenation venous cannula across the interatrial septum into the left atrium and the presence of a clot within the cannula's lumen. Transesophageal echocardiography also guided the withdrawal of the cannula into the inferior vena cava.

A novel multimedia workshop on portable cardiac critical care ultrasonography: a practical option for the busy intensivist.

We aimed to assess the role of a short duration multimedia workshop to improve the knowledge and skills in cardiac critical care ultrasonography. Thirty critical care physicians participated in the cardiac critical care ultrasonography workshop. Two weeks prior to hands-on training, a three-hour web-based didactic lecture was provided to learners. Hands-on training consisted of a two-hour examination on models without pathology and a 30-minute debriefing with instructors. Pre- and post-workshop knowledge tests were conducted online using 30 multiple choice questions. Pre- and post-workshop skill tests were video captured for evaluation by two reviewers to whom data were masked. Scores were based on 34 predetermined checklist items including learner performance, instrumentation and adequacy of ultrasound images. Learners' confidence levels on image acquisition were assessed using a ten-point Likert scale. A short duration multimedia, hands-on workshop improved intensivists' knowledge, skills and confidence levels on cardiac critical care ultrasonography image acquisition. Further studies are needed to assess the sustainability of observed improvements. This module may be a practical option for the acquisition and maintenance of cardiac critical care ultrasonography knowledge and skills.

Peripartum cardiomyopathy.

We report a case of peripartum cardiomyopathy (PPCM) with a literature review. Although PPCM is an uncommon form of cardiomyopathy, it sometimes occurs in women of childbearing age and thus should be considered in a woman who develops heart failure in the peripartum period. The diagnosis is based on a compatible clinical picture and exclusion of other potential causes. Risk factors include being black, over 30 years old, and multiparous, as well as having preeclampsia or hypertension or a multiple birth. The cause is unknown but may be multifactorial. Treatment is similar to that for other dilated cardiomyopathies; steroids and immunosuppressive agents may be useful in some circumstances. Outcome is variable with a long-term survival rate of about 50%. Patients who survive usually have few symptoms.

Evaluation of the potential role of color-coded tissue Doppler echocardiography in the detection of allograft rejection in heart transplant recipients.

BACKGROUND: Color-coded tissue Doppler (TD) echocardiography can noninvasively quantify alterations in left ventricular (LV) systolic and diastolic function. The objective of this study was to test the hypothesis that TD may play a role in the detection of LV dysfunction associated with allograft rejection in heart transplant recipients. METHODS AND RESULTS: Seventy-eight consecutive transplant recipients underwent 89 TD studies of posterior wall myocardial velocity gradient and mitral annular velocity within 1 hour of endomyocardial biopsy. Color TD echocardiographic images were digitized for semiautomated computer analysis. Histologic analysis revealed no significant rejection in 75 biopsies and significant rejection in 14. TD posterior wall peak systolic and diastolic velocity gradients were reduced significantly with rejection: 3.9 +/- 2.0 s(-1) versus 2.6 +/- 0.9 s(-1) and 5.4 +/- 2. 4 s(-1) versus 3.5 +/- 1.6 s(-1), respectively (P <.05 vs the nonrejecting group). Peak systolic and diastolic mitral annular velocities by TD were also reduced with rejection: 63 +/- 14 mm/s versus 49 +/- 12.4 mm/s and 90 +/- 23 mm/s versus 60 +/- 21 mm/s, respectively (P <.001 vs the nonrejecting group). A TD peak-to-peak mitral annular velocity >135 mm/s had 93% sensitivity, 71% specificity, and 98% negative predictive value for detecting rejection. Although TD was unable to discriminate between rejection and other causes of low velocity values, high TD velocity values were supportive of excluding rejection. CONCLUSIONS: These data suggest that color-coded TD may play a potential role as a screening test to exclude rejection in heart transplant recipients. Although this method has the potential to decrease the number of biopsies, further testing in a larger series of transplant recipients with rejection is warranted.