Proportion and risk factors of cholesterol crystal embolization after cardiovascular procedures: a retrospective national database study.

Cholesterol crystal embolization (CCE) is a rare, mainly iatrogenic condition. The proportion of CCE after cardiovascular procedures has not been fully elucidated. The purpose of this study was to determine the proportion of CCE diagnosed after cardiovascular procedures and to identify risk factors for CCE occurrence. Data on patients aged older than 40 years who underwent cardiovascular procedures between July 2010 and March 2017 were extracted from the Japanese Diagnosis Procedure Combination database. Inpatients diagnosed with CCE within 1 year after procedures in the same hospital were identified. Logistic regression analysis was performed to identify factors associated with the occurrence of CCE. There were 962 patients with CCE in 2,190,300 patients who underwent cardiovascular procedures. The overall proportion of CCE after cardiovascular procedures was 4.4 per 10,000 patients (95% confidence interval 4.1-4.7). The overall in-hospital mortality among patients with CCE was 11% (107/962). Older age, male sex, smoking, heart failure, peripheral vascular disease, cerebrovascular disease, renal insufficiency, diabetes mellitus, hypertension, and aortic aneurism and dissection were significantly associated with the higher occurrence of CCE. Compared with cardioangiography, several procedures were significantly associated with higher occurrence of CCE, including intra-aortic balloon pumping, percutaneous transluminal angioplasty of the renal artery, and transcatheter aortic valve implantation or balloon aortic valvuloplasty. CCE is rare but remains a severe complication of cardiovascular procedures. Atherosclerotic risk factors and certain cardiovascular procedures were associated with CCE.

Atheroembolic renal disease with rapid progression and fatal outcome.

Atheroembolic renal disease is caused by foreign-body reaction to cholesterol crystals flushed from the atherosclerotic plaques into the small-vessel system of the kidneys. It is an underdiagnosed entity, mostly related to vascular procedures and/or anticoagulation, and prognosis is considered to be poor. Besides the benefit of aggressive medical prevention of further embolic events, use of steroid therapy has been associated with greater survival. Here we report a case of a patient with a multisystemic presentation of the disease days after performance of percutaneous coronary intervention and anticoagulation initiation due to an episode of myocardial infarction. Renal, cutaneous, ophthalmic, neurological, and possibly muscular and mesenteric involvement was diagnosed. Although medical treatment with corticosteroids and avoidance of further anticoagulation was applied, the patient rapidly progressed to end-stage renal disease requiring hemodialysis and died 6 months after diagnosis. This is a case of catastrophic progression of the disease resistant to therapeutic measures. Focus on diagnosis and more efficient preventive and therapeutic protocols are therefore needed.

Renal function, atherothrombosis extent, and outcomes in high-risk patients.

BACKGROUND: Although prior data showed an association between chronic kidney disease (CKD) and atherothrombotic events, little is known about the risk profile and specific outcomes of atherothrombotic outpatients with CKD. METHODS: More than 69,000 outpatients at risk of atherothrombotic events were enrolled in the REACH Registry. Creatinine clearance (CrCl) was available for 51,208 patients divided into 4 groups: normal (CrCl > or =90 mL/min, n = 13,949), mild (60-89 mL/min, n = 19,474), moderate (30-59 mL/min, n = 15,883), and severe CKD (CrCl <30 mL/min, n = 1902). Baseline characteristics, number of arterial beds overtly affected, medications, overall mortality, cardiovascular death, myocardial infarction, stroke, congestive heart failure, peripheral arterial events, and bleeding events were assessed according to renal function. RESULTS: The number of arterial beds affected increased with severity of CKD. However, patients with severe CKD were less likely to receive medications of proven benefit. Severe CKD was an independent correlate of all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, peripheral arterial revascularization, or amputation. CONCLUSION: One third of outpatients at risk for atherothrombotic events have moderate to severe CKD. They are less likely to receive beneficial therapies despite a higher atherothrombotic burden and worse outcomes.

The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors.

BACKGROUND: Atheroembolic renal disease (AERD) is caused by showers of cholesterol crystals released by eroded atherosclerotic plaques. Embolization may occur spontaneously or after angiographic/surgical procedures. We sought to determine clinical features and prognostic factors of AERD. METHODS AND RESULTS: Incident cases of AERD were enrolled at multiple sites and followed up from diagnosis until dialysis and death. Diagnosis was based on clinical suspicion, confirmed by histology or ophthalmoscopy for all spontaneous forms and for most iatrogenic cases. Cox regression was used to model time to dialysis and death as a function of baseline characteristics, AERD presentation (acute/subacute versus chronic renal function decline), and extrarenal manifestations. Three hundred fifty-four subjects were followed up for an average of 2 years. They tended to be male (83%) and elderly (60% >70 years) and to have cardiovascular diseases (90%) and abnormal renal function at baseline (83%). AERD occurred spontaneously in 23.5% of the cases. During the study, 116 patients required dialysis, and 102 died. Baseline comorbidities, ie, reduced renal function, presence of diabetes, history of heart failure, acute/subacute presentation, and gastrointestinal tract involvement, were significant predictors of event occurrence. The risk of dialysis and death was 50% lower among those receiving statins. CONCLUSIONS: Clinical features of AERD are identifiable. These make diagnosis possible in most cases. Prognosis is influenced by disease type and severity.

Cholesterol embolism: still an unrecognized entity with a high mortality rate.

BACKGROUND: Cholesterol embolism (CE) is an increasingly common but often underdiagnosed medical problem. The recognition of clinical manifestations of CE is the first step toward a correct diagnosis. OBJECTIVE: Our aim was to characterize the features of CE and the risk factors for fatal outcome. METHODS: Clinical records of patients with clinical and histopathologic diagnoses of CE seen from January 1993 through March 2003 were reviewed. RESULTS: Twenty-six male patients were identified. Mean age was 64 years (range, 48-88 years). All patients had two or more risk factors for atherosclerosis. All but one patient had preexisting symptomatic atherosclerotic disease. At least one precipitating factor was identified in 23 patients (88%). Diagnosis of CE at admission was made in 9 patients only (35%). Cutaneous lesions (88%) and renal failure (73%) were the most common clinical findings. Complications (dialysis, acute pulmonary edema, amputation, or gastrointestinal surgery) were present in 21 patients (81%), and 15 patients died (58%). Previous chronic renal failure was the only variable associated with mortality (relative risk: 4.54, 95% confidence interval 1.26-16.6; P = .02). LIMITATIONS: The results were obtained from patients admitted to a university hospital. This fact may have selected a higher proportion of severe cases. CONCLUSIONS: CE was frequently misdiagnosed. Skin lesions were the most common clinical findings and skin biopsy provided histologic confirmation in most of the patients. Chronic renal failure was the only factor related to death.

Atheroembolic renal failure after invasive procedures. Natural history based on 52 histologically proven cases.

Atheromatous plaque material containing cholesterol crystals may dislodge and cause distal ischemia. To characterize atheroembolic renal failure, we retrospectively evaluated all patients at the Massachusetts General Hospital from 1981 to 1990 with both renal failure and histologically proven atheroembolism after angiography or cardiovascular surgery. Over the 10-year period, 52 patients were identified. They tended to be elderly men with a history of hypertension (81%), coronary artery disease (73%), peripheral vascular disease (69%), and current smoking (50%). Within 30 days of their procedure, only 50% of patients had cutaneous signs of atheroembolism, and 14% had documented blood eosinophilia. Urinalysis was often abnormal. Hemodynamically unstable patients died shortly after their procedure, yet renal function in the remainder continued to decline over 3 to 8 weeks. Patients who received dialysis had a higher baseline serum creatinine than those who did not (168 +/- 44 mumol/L versus 133 +/- 18 mumol/L, p = 0.02), with dialysis starting a median of 29 days after the procedure. Patients with renal failure due to atheroembolism alone, as opposed to multiple renal insults, were more likely to recover renal function (24% versus 3%, p = 0.03) and had a lower risk of death during the 6 months after their procedure (log-rank p = 0.002). Renal failure due to procedure-induced AE is characterized by a decline in renal function over 3 to 8 weeks. This time course is not consistent with most other iatrogenic causes of renal failure, such as radiocontrast or nephrotoxic medications, which present earlier and often resolve within 2 to 3 weeks after appropriate intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Atheroembolism in cardiac surgery.

BACKGROUND: Atheroembolism is a recognized complication of cardiac surgery, but its incidence and various outcomes have not been completely described. A retrospective study was undertaken to better characterize the syndrome. METHODS: Records of 49,377 autopsies and surgical specimens from the Johns Hopkins Hospital between 1973 and 1995 were reviewed. Three hundred twenty-seven patients (0.7%) had an identifiable atheroembolism on histologic examination. Of these patients, 29 (0.2%) had undergone a cardiac surgical procedure within 30 days of autopsy or surgical resection. Patient charts and pathology specimens were reviewed for operative findings, postoperative outcomes, and histology. RESULTS: Six of the 29 patients (21%) had atheroembolism to the heart, 7 patients (24%) had embolism to the central nervous system, 19 patients (66%) had embolism to the gastrointestinal tract, 14 patients (48%) had embolism to one or both kidneys, and 5 patients (17%) had embolism to a lower extremity. Sixteen patients (55%) had atheroembolism in two or more areas. In 6 patients (21%), death was directly attributable to atheroembolism, including intraoperative cardiac failure from coronary embolism (n = 3), massive stroke (n = 2), and extensive gastrointestinal embolization (n = 1). CONCLUSIONS: Atheroembolism in cardiac surgery has a broad spectrum of clinical presentations, including devastating injuries and death. Although the true incidence is probably underestimated in this retrospective study, the high attendant mortality and morbidity of atheroembolism have been documented. Improvements in outcome are likely to be associated with preoperative identification of patients at high risk, modifications of perfusion technique, and interventions to minimize secondary thrombosis and progressive organ ischemia.

Atheroembolic renal failure requiring dialysis: potential for renal recovery? A review of 43 cases.

AIMS: Our objectives were to review the characteristics of patients who developed atheroembolic renal disease requiring dialysis as well as their renal function recovery and survival rates. METHODS: All cases of atheroembolic disease with renal failure severe enough to require dialysis were reviewed from January 1984 to December 2000 in two centers. The diagnosis of atheroemboli was based on clinical presentation and/or biopsy. Acute renal failure was defined as a serum creatinine >200 micromol/l if normal at baseline or doubling from baseline if chronic renal failure, whereas renal function recovery was the ability to discontinue renal replacement therapy for >or=3 months. RESULTS: Forty-three cases were identified (37 males and 6 females; mean age 67 +/- 5 years); the average time to acute renal failure and to diagnosis was similar at 36 days. The majority of patients had at least one precipitating factor identified (58% coronary angiography, 26% angiography, 16% vascular surgery, 2% anticoagulation); 1 had a spontaneous presentation whereas 7 had more than one factor. More than 90% had underlying hypertension and chronic renal dysfunction with a baseline creatinine of 195 +/- 81 micromol/l, approximately 80% had coronary artery disease, 80% were smokers, 60% had a history of abdominal aorta aneurysm, >50% presented with intermittent claudication, and 56% were anticoagulated at the time of the event. Most patients were nonoliguric (80%), had increased hypertension (71%), blue toes (67%), livedo reticularis (52%), whereas abdominal pain and central nervous system symptoms were present in 33 and 7% of the cases, respectively. Eosinophilia was found in 88%, while hypocomplementemia was present in less than 15%. When compared to the 12 patients with recovery of renal function (after a mean delay of 409 +/- 336 days), the 31 patients who did not recover function presented with more severe intermittent claudication and underlying chronic renal dysfunction (p < 0.05). Indeed, the only variable found to unfavorably influence renal function recovery was the presence of intermittent claudication. Patients were mainly treated by intermittent hemodialysis except for 5 (2 on CRRT and 3 on peritoneal dialysis). Renal function recovery was associated with a higher chance of survival; 33% of patients died in the first year after diagnosis. CONCLUSION: Atheroembolic renal disease carries a high mortality rate reflective of the extensive cardiovascular disease of affected patients; nevertheless, the potential for renal function recovery appears greater than for other vascular causes of renal failure.

Apheresis in the treatment of cholesterol embolic disease.

Cholesterol embolic disease is a devastating complication of atherosclerosis. Universally recommended treatment is lacking thus far. Recent data suggest that a therapeutic protocol aimed at specifically combating three causes of mortality, recurrent bouts of cholesterol embolism, cardiac failure, and cahexia, were associated with a favorable clinical outcome. As for drug therapy, corticosteroid has been reported to be beneficial in reducing local and general inflammatory responses. Concerning apheresis, combined therapy consisting of plasma exchange and low to intermediate-dose corticosteroid therapy has been shown to be effective in multivisceral cholesterol embolism. Low density lipoprotein (LDL) apheresis has been reported to be beneficial for cholesterol embolism-induced damage to the skin and brain.

Lack of association between dialysis modality and outcomes in atheroembolic renal disease.

BACKGROUND AND OBJECTIVES: Atheroembolic renal disease (AERD) can require dialytic support. Because anticoagulation may trigger atheroembolization, peritoneal dialysis may be preferred to hemodialysis. However, the effect of dialysis modality on renal and patient outcomes in AERD is unknown. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: A subcohort of 111 subjects who developed acute/subacute renal failure requiring dialysis was identified from a larger longitudinal study of AERD. The main exposure of interest was dialysis modality (peritoneal versus extracorporeal therapies). Logistic regression was used to study the probability of renal function recovery. Times from dialysis initiation to death were studied using Cox's regression. RESULTS: Eighty-six patients received hemodialysis and 25 received peritoneal dialysis. The probability of renal function recovery was similar by dialysis modality (25% among hemodialysis patients and 24% among peritoneal dialysis patients; P = 0.873). During follow-up, 58 patients died, 14 among peritoneal patients and 44 among hemodialysis patients (P = 0.705). In multivariable analysis, gastrointestinal tract involvement and use of statins maintained an independent effect on the risk of patient death. CONCLUSIONS: This study does not support the notion that one dialysis modality is superior to the other. However, the observational nature of the data precludes any firm conclusions.

The fate of patients with retinal artery occlusion and Hollenhorst plaque.

OBJECTIVE: Ocular symptoms and signs often herald hemispheric neurological events associated with extracranial cerebrovascular disease. However, the presence of a Hollenhorst plaque (HP) or retinal artery occlusion (RAO) and the risk of stroke is unclear. The purpose of this study was to review the outcomes of all patients who presented with a HP or RAO at a single institution. METHODS: Between 2000 and 2005, the management and outcome of 130 consecutive patients with a diagnosis of HP, central RAO, or branch RAO (ICD-9 codes 362.30 to 362.33) were reviewed. Patients with transient monocular visual loss (amaurosis fugax), retinal venous occlusion, and other ocular pathologies were excluded. Electronic and hardcopy medical records were reviewed for demographic data, clinical variables, radiological, and noninvasive vascular lab testing. Duplex and magnetic resonance angiography (MRA) of the carotid arteries were reviewed to confirm the presence of a lesion and quantify the degree of stenosis. RESULTS: During the study interval, 70 males and 60 females, with a mean age of 68 +/- 16 (+/-SD) years underwent ophthalmologic evaluation. Symptoms were present in 61% of patients and included eye pain, blurred vision, or atypical visual symptoms, while 39% were asymptomatic. Atherosclerotic risk factors in this population included the presence of hypertension (73%), diabetes (33%), hyperlipidemia (75%), and tobacco use (38%). A majority of patients underwent carotid interrogation via Duplex imaging (68%). Carotid bifurcation stenoses ipsilateral to the ocular findings were <30% in 68% of the patients, between 30 and 60% in 22% and >60% in only 8% of patients. Six patients with lesions greater than 60% went on to have either a carotid endarterectomy or carotid stenting. Follow-up data on this group ranged from 1 to 49 months (median, 22 months), with no stroke or transient ischemic attack identified. There were five deaths during follow-up; none related to stroke. Serial carotid Duplex examinations failed to identify progression of carotid stenoses in this group of patients. Overall survival was 94% at 36 months for this cohort. CONCLUSION: The presence of a HP or RAO is associated with a low prevalence of extracranial cerebrovascular disease that requires intervention. Furthermore, in contradistinction to amaurosis fugax, these ocular findings are not associated with a high risk for hemispheric neurological events.

Atheroembolic renal disease: effect on morbidity and survival after revascularization for atherosclerotic renal artery stenosis.

PURPOSE: Atheroembolic renal disease is increasingly found in older patients with general atherosclerosis. We evaluated the impact of atheroembolic renal disease on morbidity and survival after surgical revascularization for atherosclerotic renal artery stenosis. MATERIALS AND METHODS: The study group comprised 44 patients who underwent surgical revascularization for atherosclerotic renal artery stenosis and concomitant intraoperative renal biopsy. Renal biopsy specimens were reviewed by a pathologist and evaluated for the presence or absence of atheroemboli, and the presence and severity of arteriolar nephrosclerosis. Postoperative patient data were reviewed to evaluate survival, and the incidence of renal and systemic morbid events. Patients were followed for 1 to 14.5 years (median 6.2) after surgical revascularization. RESULTS: Atheroembolic renal disease was identified in the intraoperative biopsy specimen in 16 patients (36%, group 1) and was absent in 28 (64%, group 2), termed groups 1 and 2. Atheroembolic renal disease correlated significantly with decreased patient survival. The 5-year survival in groups 1 and 2 was 54 and 85%, respectively (p = 0.011). Similarly the incidence of systemic atherosclerotic complications was significantly higher in group 1 than group 2 (86 versus 58%, p <0.05). In addition, renal or renovascular complications developed in more group 1 than group 2 patients (p = 0.07). There was no significant association between the presence or severity of arteriolar nephrosclerosis and postoperative survival or morbid events. CONCLUSIONS: Our results indicate that atheroembolic renal disease is associated with decreased survival and an increased incidence of atherosclerotic morbid events after surgical revascularization for atherosclerotic renal artery stenosis. This information may be useful for therapeutic decision making in patients with atherosclerotic renal artery stenosis.

[Other systemic diseases in the elderly]. / Autres maladies systémiques du sujet âgé

The prevalence of systemic diseases depends on patient age. One third to one half of the patients with Wegener's granulomatosis are over 60 years at the diagnosis. In the elderly, renal insufficiency, lymphopenia and central nervous system involvement are more frequent, and upper airways involvement and hemoptysis less frequent. Signs suggestive of temporal arteritis may initiate the disease. Mortality is increased in the elderly, and aging is an independent predictor of poor prognosis. Henoch-Schönlein purpura is uncommon in adulthood; one quarter of adult cases involves an elderly patient. End-stage renal failure and association with neoplasia are common. In some cases, synchronous course of purpura and neoplasia leads to consider it as a true paraneoplastic syndrome. Periarteritis nodosa in the elderly is characterized by an increased frequency of the association with viral B hepatitis and skin vasculitis. Histological location of necrotizing arteritis involving the temporal artery is possible. It should be considered as a borderline disease, and treated as the more severe disease. Aging is predictive of poor prognosis. Cholesterol emboli are a classic complication of atheroembolic disease and may mimic an inflammatory and multisystemic disease with renal, cardiac, pulmonary, digestive, neuropsychiatric, skin and muscle involvements due to ischemic phenomena leading to necrosis. One-year mortality is over 60% in the symptomatic forms.

Surgical management of atheroembolization.

PURPOSE: Atheroembolization may cause limb loss or organ failure. Surgical outcome data are limited. We report the largest series of atheroembolization focusing on patterns of disease, surgical treatment and outcome. METHODS: One hundred patients (70 men), mean age 62 +/- 11 years, operated on for lower extremity, visceral, or nonthoracic outlet upper extremity atheroemboli were identified prospectively and monitored over a 12-year period. The atheroembolic source was localized by use of a combination of computed tomography scanning (n = 55), arteriography (n = 93), duplex scanning (n = 25), transesophageal echocardiography (n = 6), and magnetic resonance imaging (n = 4). Occlusive aortoiliac disease (47 patients) and small aortic aneurysms (20 patients; mean aneurysm size 3.5 +/- 0.8 cm) were the most common source of atheroemboli. Imaging studies revealed 12 patients with extensive suprarenal aortic thrombus. Correction of the embolic source was achieved with aortic bypass (n = 52), aortoiliac endarterectomy and patch (n = 11), femoral or popliteal endarterectomy and patch (n = 11), infrainguinal bypass (n = 3), extraanatomic reconstruction (n = 6), graft revision (n = 3), upper extremity bypass (n = 11), or upper extremity endarterectomy and patch (n = 3). RESULTS: All four deaths within 30 days and all seven deaths within the first 6 months after operation were among the 12 patients with suprarenal aortic thrombus. The cumulative survival probabilities for all patients at 1, 3, and 5 years were 89%, 83%, and 73%, respectively. After operation, nine patients required major leg amputations and 10 required toe amputations. Renal atheroemboli led to hemodialysis in 10 patients. Recurrent embolic events occurred in five of 97 patients monitored for a mean of 32 months. All five recurrences occurred in the first 8 months after operation. Three patients with recurrent emboli had suprarenal aortic disease, one of whom had undergone axillofemorofemoral bypass. Four of 15 patients receiving postoperative warfarin anticoagulation had development of recurrent embolism. Only one patient not receiving postoperative warfarin had a recurrent event (p < 0.05 by Fisher exact test). CONCLUSION: The atheroembolic source is the aorta or iliac arteries in two thirds of patients who underwent operation. Computed tomography scanning of the aorta is a useful diagnostic technique. The source of the emboli can be eliminated surgically with low mortality or limb loss rates except when the suprarenal aorta is involved.

Cholesterol crystal embolization: an atherosclerotic disease with frequent and varied cutaneous manifestations.

In this paper the basic pathogenesis of cholesterol crystal embolization (CCE) is described, its clinical characteristics are presented and diagnosis and therapy are discussed. The main focus will be on the cutaneous manifestations; however, considering that CCE is a systemic illness, findings in other organs will also be highlighted, particularly the commonly involved renal and gastrointestinal systems.