Angioplasty and stenting of the extracranial carotid arteries.

We performed percutaneous transluminal angioplasty and stenting in patients with carotid artery stenosis to determine the efficacy of these techniques as an alternative to surgical endarterectomy. From April 1995 through July 1999, 315 carotid angioplasty procedures were performed (right, 151; left, 164) in 290 patients ranging in age from 40 to 93 years. Of these patients, 42% were symptomatic and 58% were asymptomatic. Twenty-five patients underwent bilateral procedures. The mean percentage of stenosis was 82.3%+/-8.7% SD. Angioplasty and stenting were performed without cerebral protection in 165 arteries and with protection in 150. Two methods of protection were used: the Theron technique and the PercuSurge Guardwire temporary occlusion and aspiration system. Balloon dilation and stent placement were successful in 289 patients; in the last patient, severe arterial tortuosity prevented catheterization and stenting. We observed 13 periprocedural neurologic complications due to ischemia (4.2%): 4 transient ischemic attacks (1.3%), 4 minor strokes (1.3%), and 5 major strokes (1.6%), including 1 death. At 6 months, 210 patients had a follow-up angiogram (155) or duplex ultrasound (55). There were 10 restenoses (4.7%), 1 of which was symptomatic and 2 of which showed mild compression of a Palmaz stent without marked stenosis. Primary and secondary 4-year patency rates were 96% and 99%, respectively. These results demonstrate acceptable mortality and morbidity rates related to carotid angioplasty and stenting. However, we found the risk of embolic stroke to be substantial. Cerebral protection may improve the results of carotid angioplasty and expand the indications for this procedure.

Percutaneous transluminal angioplasty of the subclavian arteries.

PURPOSE: To review the feasibility, risks, and long-term results of subclavian artery angioplasty with and without Palmaz stent placement. METHODS: Over a 9-year period, 113 patients (67 males; mean age 63 +/- 13 years) underwent percutaneous balloon angioplasty of subclavian occlusive lesions for a variety of indications: vertebrobasilar insufficiency (n = 70), upper limb ischemia (n = 50), coronary steal syndrome (n = 6), or anticipated coronary artery bypass grafting using the internal mammary artery in 12 asymptomatic patients. There were 94 (83%) stenoses and 19 (17%) occlusions with a mean percent stenosis of 80.1% +/- 7.4% (range 70 to 100). Mean lesion length was 24 +/- 8 mm (range 10 to 50). Beginning in 1989, stents were implanted for suboptimal dilation; in 1995, stenting became routine. RESULTS: Overall, 103 (91%) of 113 lesions were successfully treated; 10 (53%) occlusions could not be recanalized. Fifty-one stents were implanted in 46 patients. There were 3 (2.6%) procedural complications: a transient ischemic attack, one major (fatal) stroke, and an arterial thrombosis 24 hours after the procedure (treated medically) (0.9% major stroke and death rate). During a mean 4.3-year follow-up (range to 10), 16 (15.5%) restenoses were treated with angioplasty (n = 4), stenting (n = 7), or surgery (n = 5). Primary and secondary patencies for all treated lesions (n = 113) at 8 years were 75% and 81%, respectively; in patients without initial stent placement, the rates were 69% and 76%, while in those with stents, the rates rose slightly to 87% and 94% at 2.5 years (NS). Patency rates for all 103 recanalized lesions were 83% and 90% at 8 years (81% and 90% without stent and 87% and 94% with stent at 2.5 years, respectively [NS]). CONCLUSIONS: Balloon angioplasty with or without stenting is safe and effective for treating subclavian artery occlusive diseases with good long-term patency. Recanalization of occlusions is more difficult to achieve. Stents (implanted only for suboptimal dilation) do not seem to improve long-term patency.

Stents in the treatment of renal artery stenosis: long-term follow-up.

PURPOSE: To evaluate the role of percutaneous stenting in the treatment of renal arterial lesions after failure of balloon angioplasty. METHODS: Two hundred ten patients (139 males; mean age 67.7 +/- 9.9 years, range 27 to 87) had 259 balloon-expandable stents (165 Palmaz and 94 Renal Bridge stents) implanted in 244 renal artery stenoses (171 ostial and 73 nonostial lesions). The patients were suffering from intractable hypertension (n = 210) and/or renal dysfunction (n = 48). The majority of the lesions (n = 234) were atheromatous in origin. Stents were implanted for suboptimal balloon dilation (n = 182, 75%), restenotic lesions (n = 27, 11%), or dissection (n = 9, 4%); 26 (11%) ostial lesions were stented primarily. Mean lesion length was 11.9 +/- 4.4 mm (range 5 to 30) and mean percent stenosis was 81.9% +/- 8.25% (range 70 to 100). RESULTS: Immediate technical success was 99% (241 of 244). Three (1.2%) major complications included one intraprocedural stent thrombosis, one arterial perforation manifesting as a perirenal hematoma 24 hours after the procedure, and one renal arterial rupture. Follow-up over a mean 25.4 +/- 22.8 months (range 1 to 96) in 185 eligible patients (209 arteries) found 24 cases of restenosis (11.4%). Primary and secondary patencies for all lesions at 60 months were 79% and 98%, respectively, with no significant differences between ostial and nonostial lesions or stent types. Hypertension was reversed in 35 (19%), improved in 112 (61%), and remained unchanged in 37 (20%). Renal function was improved in 29% (14 of 48), unchanged in 67% (32 of 48), and worse in 4% (2 of 48). CONCLUSIONS: Renal artery stenting is safe, effective, and may be an alternative to surgery, particularly in ostial lesions. Our experience shows reduction in the restenosis rate compared to conventional angioplasty. All ostial stenoses should be stented.

Carotid stenting with cerebral protection: first clinical experience using the PercuSurge GuardWire system.

PURPOSE: To study the feasibility and safety of carotid angioplasty and stenting using a new cerebral protection device that temporarily occludes the distal internal carotid artery (ICA). METHODS: Forty-eight high-risk patients (39 men, mean age 69.1 +/- 8 years, range 54 to 86) with 53 ICA stenoses underwent percutaneous angioplasty and stenting via the femoral approach under cerebral protection afforded by a 0.014-inch GuardWire balloon occlusion device. Mean stenosis was 82.1% +/- 9.65% (range 70 to 96) and mean lesion length was 16.0 +/- 7.5 mm (range 6 to 50). Thirty-three (62%) lesions were calcified, and 38 (72%) were ulcerated. Thirty-two (60%) of the lesions were asymptomatic. With the occlusion balloon inflated in the distal ICA, the lesion was dilated and stented. The area was cleaned by aspiration and flushed via an aspiration catheter advanced over the wire. Blood samples were collected from the external carotid artery (ECA) and analyzed to measure the size and number of particles collected. Computed tomography and neurological examinations were performed the day after the procedure. RESULTS: Immediate technical success was achieved in all patients with the implantation of 38 Palmaz stents, 8 Expander stents, and 11 Wallstents. Carotid occlusion was well tolerated in all patients but 1 who had multiple, severe carotid lesions and poor collateralization. Mean cerebral flow occlusion time was 346 +/- 153 seconds during predilation and 303 +/- 143 seconds during stent placement. Total mean flow occlusion time was 542 +/- 243 seconds. One immediate neurological complication (transient amaurosis) occurred in a patient who had an anastomosis between the external carotid (EC) and ICA territories. Debris was removed in all patients with a mean 0.8-mm diameter catheter. CONCLUSION: Cerebral protection with the GuardWire device is easy, safe, and effective in protecting the brain from cerebral embolism. Larger studies are warranted.

Angioplasty and stenting of the extracranial carotid arteries.

PURPOSE: To study the feasibility and safety of stent-supported angioplasty in the treatment of atherosclerotic stenoses of the extracranial carotid arteries. METHODS: Carotid angioplasty was attempted in 174 arteries (163 patients: 126 males; mean age: 71 +/- 10 years, range 47 to 93). Mean lesion length was 15.1 +/- 4.1 mm, and mean percent stenosis was 83.8% +/- 7.3% (reference diameter 5.8 +/- 0.7 mm). The majority (106, 65%) were asymptomatic (51% of all patients had severe coronary disease, 32% had peripheral vascular diseases). Patients underwent independent neurological examination, computed tomography, duplex ultrasonography, and angiography preprocedurally, 24 hours after the procedure, and at 6-month follow-up intervals. Most (142, 82%) carotid arteries were treated without cerebral protection, but a protective triple coaxial catheter was used in 32 (18%) patients. Stents (primarily Palmaz and Wallstent) were deployed routinely in all cases; 18% were implanted without predilation. RESULTS: Immediate technical success was 173 of 174 (99.4%) (1 access failure referred electively to surgery). Eight (4.6%) neurological complications occurred in the periprocedural period: 3 transient ischemic attacks, 2 minor strokes, and 3 major strokes (1 amaurosis and 2 hemiplegias). Two major complications developed despite cerebral protection. There were no deaths or myocardial infarctions and only 3 cervical access site hematomas. Over a mean 12.7 +/- 9.2 month follow-up (range 1 to 36), no ipsilateral neurological complications have been seen. There were 4 (2.3%) restenoses (3 redilated, 1 treated medically) and 1 mild Palmaz stent compression, all found within the first 6 months. Primary and secondary patencies at 3 years are 96% and 99%, respectively. CONCLUSIONS: Angioplasty with routine stenting seems feasible and safe for treating certain types of carotid stenoses even in high-surgical risk patients; however, randomized trials are necessary before this treatment can be offered as an alternative to endarterectomy.

Differential effects of fosinopril and enalapril in patients with mild to moderate chronic heart failure. Fosinopril in Heart Failure Study Investigators.

OBJECTIVES: To investigate the efficacy and safety of fosinopril in the treatment of chronic heart failure (CHF), patients with mild to moderate CHF and left ventricular ejection fractions <40% were randomly assigned in a double-blind manner to receive fosinopril 5 to 20 mg every day (n = 122) or enalapril 5 to 20 mg every day (n = 132) for 1 year. RESULTS: The event-free survival time was longer (1.6 vs 1.0 months, P= .032) and the total rate of hospitalizations plus deaths was smaller with fosinopril than with enalapril (19.7% vs 25.0%, P= .028). There was consistently better symptom improvement with fosinopril (P< .05). The incidence of orthostatic hypotension was lower in the fosinopril group (1.6% vs 7.6%, P< .05). CONCLUSIONS: Fosinopril 5 to 20 mg every day was more effective in improving symptoms and delaying events related to worsening of CHF and produced less orthostatic hypotension than enalapril 5 to 20 mg every day.

Abnormal transoesophageal Doppler coronary flow reserve in patients with dilated cardiomyopathy: relationship to exercise capacity.

1. In patients with dilated cardiomyopathy, abnormal myocardial blood flow may contribute to poor myocardial function. 2. The aim of this study was to investigate the possible contribution of abnormal myocardial blood flow to the limitation of exercise capacity in patients with dilated cardiomyopathy. 3. Coronary flow reserve was assessed in 16 patients with dilated cardiomyopathy and 9 matched normal control individuals. All participants had angiographically normal coronary arteries. At rest and after dipyridamole infusion (0.56 mg/kg intravenously), peak systolic and diastolic coronary flow velocities were measured in the proximal left anterior descending coronary artery using transoesophageal pulsed Doppler echocardiography, guided by colour flow imaging. Coronary flow reserve was calculated as the ratio of hyperaemic to basal diastolic and systolic peak coronary flow reserve. 4. Baseline diastolic and systolic coronary flow velocities were significantly higher in patients (50 +/- 6 and 30 +/- 4 cm/s respectively) compared with control individuals (37 +/- 3 and 20 +/- 1 cm/s respectively) (mean +/- S.E.M.) (P < 0.05). Diastolic and systolic peak coronary flow reserve were significantly lower in patients (1.60 +/- 0.14 and 1.40 +/- 0.09 respectively) compared with control individuals (2.89 +/- 0.15 and 2.17 +/- 0.17 respectively) (P < 0.001). Although peak VO2 and exercise time were significantly lower in patients compared with control individuals, coronary flow reserve did not correlate to exercise capacity in patients with dilated cardiomyopathy. 5. These results confirm the abnormalities of coronary flow reserve previously observed in patients with dilated cardiomyopathy, but suggest that such abnormalities do not contribute to the limitation of exercise capacity in these patients.

Physical activity, skeletal muscle beta-adrenoceptor changes and oxidative metabolism in experimental chronic heart failure.

In chronic heart failure (CHF), changes in sympathetic nervous activity and skeletal muscle metabolism contribute to a limitation in the capacity for exercise. The aim of this study was to investigate the potential relationships between physical deconditioning, skeletal muscle beta-adrenoceptor (beta-AR) characteristics and muscle metabolic changes in rats with coronary ligation-induced experimental CHF. Muscle beta-AR and norepinephrine levels were assessed in rats with CHF that had been treated with propranolol at 28 mg/kg/day and compared with rats with CHF that had not been treated and those that had undergone sham operations. The soleus muscle was investigated because of its predominantly oxidative fibre-type composition. Measurements of spontaneous locomotion activity were carried out using telemetry. After 85 days, muscle energetic phosphate levels were assessed using 31P-magnetic resonance spectroscopy. The phosphocreatine resynthesis rate was decreased in the untreated CHF rats (15 +/- 3 vs 33 +/- 5 mmol L-1 min-1 in the sham-operated rats, p < 0.05), but this had been partially reversed in the rats given propranolol (22 +/- 3 mmol L-1 min-1, non-significant (NS) when compared with the sham-operated rats). Spontaneous activity did not differ among the three groups of animals. Soleus beta-adrenoceptor density was decreased in rats with CHF (8.8 +/- 3.0 fM/mg of protein vs 22.0 +/- 7.0 fM/mg of protein in the sham-operated rats, p < 0.05) and normalized in the propranolol-treated rats (31.9 +/- 7.0 fM/mg of protein, NS vs the sham-operated rats; p < 0.05 vs the untreated rats with CHF). Unchanged spontaneous activity in the rats with CHF suggests that physical deconditioning could not account for the muscle metabolic changes. Changes in skeletal muscle energy metabolism were accompanied by changes in beta-AR density, occurring in typically oxidative beta-AR-rich muscles, reversible after beta-blocker therapy and therefore suggestive of beta-AR downregulation.

Plasma levels of atrial natriuretic peptide and of other vasoconstricting hormones in patients with chronic heart failure: relationship to exercise capacity.

We investigated the relationship between exercise capacity and the level of neurohormonal activation at rest and during exercise in patients with various degrees of severity of chronic heart failure. We performed exercise testing with measurements of peak oxygen consumption (pVo2) and blood sampling at rest and at peak exercise in eight patients with moderate heart failure (pVo2 = 17 +/- 0.4 ml/kg/min) (mean +/- S.E.M.) and eight patients with severe CHF (pVo2 = 9 +/- 1 ml/kg/min). None of the patients was taking angiotensin converting enzyme inhibitors or beta-blockers. Plasma levels of atrial natriuretic peptide, cGMP, arginine-vasopressin, renin, angiotensin II, epinephrine and norepinephrine increased significantly (P < 0.01), from rest to peak exercise, in all patients. Among all the studied neurohormonal factors, only atrial natriuretic peptide levels at rest as well as at peak exercise, in patients with severe heart failure were correlated significantly to pVo2 (r = -0.77, P = 0.04; r = -0.85, P = 0.01, respectively) and to exercise duration (r = -0.72, P = 0.05; r = -0.79; P = 0.03, respectively). The relationship between plasma levels of atrial natriuretic peptide and of cGMP was shifted downward in the more severe patients suggesting the loss of biological activity of atrial natriuretic peptide.

Skeletal muscle beta-adrenoreceptors and phosphate metabolism abnormalities in heart failure in rats.

To investigate the mechanisms leading to skeletal muscle metabolic abnormalities in chronic heart failure (CHF), we studied phosphate metabolism and skeletal muscle beta-adrenoreceptors (beta-AR) in rats 12-14 wk after coronary ligation (CL). We performed 31P magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produced by electrical stimulation (5 Hz). The initial slope of phosphocreatine (PCr) depletion was higher in the CL rats compared with sham-operated rats (Pi/PCr/time: 0.211 +/- 0.045 vs. 0.113 +/- 0.029; P < 0.05). During recovery, both PCr resynthesis rate and maximal rate of oxidative ATP synthesis were reduced threefold in the CL rats compared with controls (11 +/- 2 vs. 37 +/- 7 mmol.l-1.min-1, P < 0.04; and 20 +/- 3 vs. 79 +/- 18 mmol.l-1.min-1, P < 0.03, respectively). There were no significant differences either for the skeletal muscle density (13 +/- 6 vs. 15 +/- 3 fM/mg) or for the affinity (0.244 +/- 0.149 vs. 0.246 +/- 0.146 nM) of beta-AR between the two groups. This study showed that, although in moderate CHF skeletal muscle metabolic abnormalities can be demonstrated, these changes could not be explained by skeletal muscle beta-adrenergic receptor alterations in this experimental model.

Physical deconditioning may be a mechanism for the skeletal muscle energy phosphate metabolism abnormalities in chronic heart failure.

The aim of our study was to investigate the contribution of physical deconditioning in skeletal muscle metabolic abnormalities in patients with chronic heart failure (CHF). Phosphate metabolism was studied in the leg muscle at rest and during exercise by using phosphate 31 nuclear magnetic resonance spectroscopy in a group of 14 patients with New York Heart Association class II and III CHF and left ventricular ejection fraction <40% and in two groups of age-matched healthy volunteers: one group of 7 sedentary and another of 7 trained subjects. Phosphocreatine depletion rate, intracellular pH, and adenosine diphosphate levels in the muscle during exercise were not statistically different in the CHF patients and in the sedentary healthy subjects, but both groups were statistically different from the trained healthy subjects, who had slower phosphocreatine depletion rates, as well as less intracellular acidosis and lower adenosine diphosphate levels during exercise (p = 0.02; analysis of variance). Our results suggest that metabolic changes occurring in the skeletal muscle of patients with CHF may contribute to the limitation of exercise capacity and are most likely to be a consequence of physical deconditioning because they are very similar to what is observed in sedentary and otherwise healthy subjects as compared with trained subjects.

Skeletal muscle phosphate metabolism abnormalities in volume-overload experimental heart failure.

We studied skeletal muscle phosphate metabolism abnormalities to examine their contribution at an early stage of congestive heart failure (CHF) in rats with aortocaval fistula (ACF) 4 wk after the procedure. In a group of 26 rats (13 with ACF and 13 sham operated), we assessed the degree of CHF. The ACF produced a significant rise in heart weight and plasma atrial natriuretic peptide. In a second group of 26 rats (13 ACF and 13 sham operated), we performed 31P-magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produced by electrical stimulation. The rate of phosphocreatine depletion, expressed by its initial slope, was higher in the ACF rats compared with controls (0.078 +/- 0.01 vs. 0.041 +/- 0.007; P < 0.03). pH and ATP decreased and phosphodiesters increased in all rats during electrical stimulation, with no difference between ACF rats and controls. The kinetics of phosphocreatine recovery were not different between ACF rats and controls. Together with previous studies, our present results suggest that muscle metabolism abnormalities in CHF may vary according to the experimental model and may be observed early in the course of the disease.

Contribution of specific skeletal muscle metabolic abnormalities to limitation of exercise capacity in patients with chronic heart failure: a phosphorus 31 nuclear magnetic resonance study.

Several studies of phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) have demonstrated the presence of skeletal muscle metabolic abnormalities during exercise in patients with chronic heart failure (CHF). We studied the contribution of these abnormalities to the limitation of exercise capacity in CHF. In 25 patients (age 57 +/- 2 years, left ventricular ejection fraction [LVEF] 28% +/- 1.6%, peak oxygen consumption (VO2) 16 +/- 1.2 ml/kg/mm) (mean +/- SEM), we studied the calf muscle at rest and during plantar flexion with 31P MRS. The phosphocreatine (PCr) depletion rate was significantly negatively correlated to peak VO2 (r = -0.62, p = 0.001) but not to LVEF. Muscle pH was correlated with the inorganic phosphorus (Pi)/PCr ratio (r = -0.69, p = 0.0001) and with the PCr/adenosine triphosphate beta (ATP beta) ratio (which negatively relates to adenosine diphosphate [ADP] concentration) (r = 0.65, p = 0.00001). Although muscle ATP (ATP/sum of phosphorus [sigma P] remained stable, in 8 patients ATP/sigma P decreased significantly (-15% +/- 4%, p = 0.0002). In this ATP-depleted group, peak VO2 was significantly lower than that of the nondepleted group and PCr depletion more rapid, whereas LVEF did not differ. Skeletal muscle metabolic abnormalities in CHF contribute markedly to the alteration of exercise capacity. Rapid PCr depletion and muscle acidosis are the most relevant abnormalities. ATP depletion and excessive increase in ADP during exercise may contribute further to exercise limitation specifically in patients with more marked CHF.

[Metabolic, morpho-histologic and biochemical changes in skeletal muscles in chronic cardiac failure]. / Les altérations métaboliques, morpho-histologiques et biochimiques du muscle squelettique dans l'insuffisance cardiaque chronique.

The study of skeletal muscle by nuclear magnetic resonance (NMR) 31p in patients with chronic heart failure (CHF) or in experimental animal models has not shown metabolic abnormalities under basal conditions. However, during exercise, phosphocreatinine (PCr) depletion is increased and early intracellular acidosis has been demonstrated. These changes contribute to deterioration of exercise capacity as they are related to peak VO2 and exercise duration. Other metabolites may play an important role. The depletion of ATP at maximal exercise may be observed in some patients with severe CCF. The results of PCr recovery kinetics are contradictory. Apparently, its recovery rate is unchanged. Most biochemical and histological abnormalities are represented by a decrease in oxidative structure (type I muscular fibres, mitochondria) and in enzymatic oxidative capacity. These changes are related to the metabolic abnormalities and exercise capacity. Muscular hypotrophy alone cannot explain the metabolic changes observed in CHF. Several mechanisms could be involved, physical deconditioning probably being the most pertinent. Other factors such as neurohormonal activation and insulin resistance should be investigated. Physical training improves exercise capacity and may reverse these muscular abnormalities. A long-term benefit of physical training on morbidity and mortality should be demonstrated.