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Biomedical subjects

Barry F Uretsky

Publications and source records attributed to Barry F Uretsky.

At least 19 recordsLinked to original sources

Sudden death prophylaxis in heart failure.

Sudden cardiac death (SCD) is the leading cause of mortality in heart failure (HF). Today the implantable cardioverter-defibrillator (ICD) has become a commonplace therapy around the world for patients with both ischemic and non-ischemic cardiomyopathy and an ejection fraction (EF) < or = 35%. However, EF alone does not discriminate between the modes of death from HF (sudden arrhythmic death vs. non-sudden death). Other risk statifiers, such as electrophysiologic study and microvolt T-wave alternans testing, should therefore be used in the appropriate settings to minimize the number of unnecessary device implants. In addition, left ventricular mechanical dyssynchrony has now become recognized as an additional major marker of cardiac mortality. Its assessment should entail echocardiography rather than measurement of the QRS duration. This will allow us to better integrate the ability of cardiac resynchronization therapy (CRT) in enhancing cardiac function with the ability of an ICD in preventing SCD. This review aims to: 1) give a synthesis of the published evidence regarding the value of implantable ICDs and CRT in the primary prophylaxis of SCD in HF; 2) discuss controversial clinical issues in this area; and 3) recommend practical device-based management strategies.

Death, Sudden, Cardiac↗

Prevention of contrast induced nephropathy: recommendations for the high risk patient undergoing cardiovascular procedures.

Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality. Chronic kidney disease is the primary predisposing factor for CIN. As estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk. Modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration. The cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion. In the patient at increased risk for CIN it is often appropriate to withhold potentially nephrotoxic medications, and consider the use of n-acetylcysteine. In patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal.

Contrast Media↗

Grade 3 ischemia on admission electrocardiogram and chest pain duration predict failure of ST-segment resolution after primary percutaneous coronary intervention for acute myocardial infarction.

OBJECTIVES: ST resolution (STR) is a surrogate marker of myocardial tissue reperfusion and a predictor of outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI). Terminal QRS distortion (grade 3 ischemia) has been shown to predict failure of STR after thrombolysis for STEMI, but the ability of grade 3 ischemia to predict STR with pPCI is unclear. METHODS: We retrospectively analyzed 155 patients who underwent pPCI and compared grade 2 ischemia (ST elevation without terminal QRS distortion; n = 89) to grade 3 ischemia (n = 66) on admission for baseline characteristics, in-hospital course, and STR immediately after pPCI and at 18 to 24 hours. RESULTS: Patients with grade 3 ischemia were older (60 +/- 12 vs 56 +/- 11 years; P = .018), had more anterior STEMI (42% vs 17%; P = .0004), and were less often smokers (41% vs 90%; P = .004). The grade 3 ischemic group had significantly less complete STR (35% vs 75% [P < .00001] immediately after pPCI and 33% vs 79% [P < .00001] 18-24 hours after pPCI), a longer hospital stay (6.4 +/- 4.1 vs 4.9 +/- 1.9 days; P = .008), and higher peak CKMB (292 +/- 231 vs 195 +/- 176 ng/mL; P = .0005). Duration of symptoms before pPCI (odds ratio [OR], 0.838; 95% confidence interval [CI], 0.724-0.969; P = .017) and grade 3 ischemia (OR, 0.181; 95% CI, 0.068-0.480; P < .001) were negative predictors of complete STR, whereas nonanterior STEMI (OR, 5.95; 95% CI, 2.154-16.436; P < .001) and initial sum of ST elevation (OR, 3.132; 95% CI, 1.140-8.605; P = .027) were positive predictors. CONCLUSION: Grade 3 ischemia on presentation of STEMI and duration of chest pain are strong independent predictors of failure to achieve complete STR after pPCI.

Angioplasty, Balloon, Coronary↗

Augmentation of myocardial production of 15-epi-lipoxin-a4 by pioglitazone and atorvastatin in the rat.

BACKGROUND: Both statins and thiazolidinediones have antiinflammatory properties. However, the exact mechanisms underlying these effects are unknown. We investigated whether atorvastatin (ATV) and pioglitazone (PIO) increase the myocardial content of lipoxin-A4 and 15(R)-epi-lipoxin-A4 (15-epi-LXA4), both arachidonic acid products with strong antiinflammatory properties. METHODS AND RESULTS: In experiment 1, rats received 3-day pretreatment with water; PIO 2, 5, or 10 mg x kg(-1) x d(-1); ATV 2, 5, or 10 mg x kg(-1) x d(-1); or PIO 10 mg x kg(-1) x d(-1)+ATV 10 mg x kg(-1) x d(-1). In experiment 2, rats received water; PIO 10 mg x kg(-1) x d(-1)+ATV 10 mg x kg(-1) x d(-1); PIO+ATV and valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor; PIO+ATV and zileuton, a selective 5-lipoxygenase inhibitor; or zileuton alone. There were 4 rats in each group. Hearts were harvested and analyzed for myocardial lipoxin-A4 and 15-epi-LXA4 levels and for COX-2 and 5-lipoxygenase protein expression. ATV and PIO at 5 and 10 mg x kg(-1) . d(-1) significantly increased myocardial 15-epi-LXA4 levels compared with the sham-treated group (0.51 +/- 0.02 ng/mg). Myocardial 15-epi-LXA4 were significantly higher in the PIO+ATV group (1.29 +/- 0.02 ng/mg; P < 0.001 versus each other group). Both valdecoxib and zileuton abrogated the PIO+ATV increase in 15-epi-LXA4, whereas zileuton alone had no effect. PIO, ATV, and their combination resulted in a small increase in myocardial lipoxin-A4 levels, which was not statistically significant. ATV alone or in combination with PIO markedly augmented COX-2 expression. PIO had a much smaller effect on COX-2 expression. Myocardial expression of 5-lipoxygenase was not altered by PIO, ATV, or their combination. CONCLUSIONS: Both PIO and ATV increase myocardial levels of 15-epi-LXA4, a mediator with antiinflammatory properties. This finding may explain the antiinflammatory properties of both PIO and ATV.

Animals↗

Role of transesophageal echocardiography guided cardioversion in patients with atrial fibrillation, previous left atrial thrombus and effective anticoagulation.

AIMS: The value of transesophageal echocardiography (TEE) to prevent cardioversion-related thromboembolic events in patients with atrial fibrillation (AF) and left atrial (LA) thrombus is unclear. We compared the embolic risk associated with a strategy of follow-up TEE-guided direct-current cardioversion (DCCV) with that of blind DCCV in patients with AF, pre-existing LA thrombus and effective anticoagulation. METHODS AND RESULTS: We identified 67 subjects with TEE-documented LA appendage thrombi from a total of 520 consecutive patients with symptomatic non-rheumatic AF who were referred to us for elective DCCV. All patients received at least 4 weeks of effective warfarin therapy (target international normalized ratio, 2 to 3) before and after DCCV. At time of DCCV, 20 patients had TEE and 47 did not. There were no clinical and echocardiographic differences between the two groups. Thrombus resolution was documented in 18 (90%) patients. After a median follow-up of 4 weeks, two transient ischemic attacks were observed in patients who were blindly cardioverted and one in patients belonging to the TEE group. Sinus rhythm was documented at the time of each thromboembolic event. By multiple logistic regression analysis the TEE strategy was not associated with lower risk of thromboembolism as compared to blind DCCV (odds ratio 1.37; 95% confidence interval, 0.16% to 15.86%; p=0.20). CONCLUSION: In patients with AF, LA thrombus and effective anticoagulation, there is no difference in the risk of clinical thromboembolism between DCCV with or without follow-up TEE. Benefits of warfarin are related to thrombus resolution and prevention of new thrombus formation.

Atrial Fibrillation↗

Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions.

We assessed 1) whether pretreatment before ischemia with pioglitazone (Pio) limits infarct size (IS) and whether this protective effect is due to nitric oxide synthase (NOS) and/or prostaglandin production, as has been shown for atorvastatin (ATV); and 2) whether Pio and ATV have synergistic effects on myocardial protection. Sprague-Dawley rats received oral ATV (10 mg.kg-1.day-1), Pio (10 mg.kg-1.day-1), their combination (Pio+ATV), or water alone for 3 days. Additional rats received Pio (10 mg.kg-1.day-1) for 3 days and intravenous SC-58125 [a cyclooxygenase-2 (COX-2) inhibitor] or SC-560 (a COX-1 inhibitor) 15 min before ischemia. Rats underwent 30 min of myocardial ischemia and 4 h of reperfusion, or hearts were harvested for analysis. IS in the Pio and in the ATV groups was significantly smaller than in the sham-treated group. IS in the Pio+ATV group was smaller than in all other groups (P<0.001 vs. each group). The protective effect of Pio was abrogated by SC-58125 but not by SC-560. Pio, ATV, and Pio + ATV increased the expression and activity of cytosolic phospholipase A2 (cPLA2) and COX-2. ATV increased phosphorylated-Akt, phosphorylated-endothelial NOS (P-eNOS), inducible NOS, and COX-2 levels. In contrast, Pio caused an insignificant increase in myocardial levels of phosphorylated-Akt but did not change P-eNOS and iNOS expression. In conclusion, the IS-limiting effects of Pio and ATV involve COX-2. However, the upstream steps differ. ATV induced eNOS phosphorylation and iNOS, cPLA2, and COX-2 expression, whereas Pio induced mainly the expression and activity of cPLA2. The effects of Pio and ATV were additive.

Animals↗

Implementation and application of a continuous quality improvement (CQI) program for the cardiac catheterization laboratory: one institution's 10-year experience.

There is consensus that a continuous quality improvement (CQI) program is essential in optimizing patient outcomes in the cardiovascular catheterization laboratory. A CQI method was described in guidelines produced by the Society for Cardiovascular Angiography and Interventions (SCAI) in 1993 and 1997. However, little information is available in the medical literature to determine the implementation and application of this approach in a modern catheterization program. This presentation describes the lessons learned from one institution's 10 year CQI experience by using the SCAI blueprint.

Cardiac Catheterization↗

Enhanced cardioprotection against ischemia-reperfusion injury with combining sildenafil with low-dose atorvastatin.

PURPOSE: Both ATV and SL reduce myocardial infarct size (IS) by enhancing expression and activity of NOS isoforms. We investigated whether atorvastatin (ATV) and sildenafil (SL) have synergistic effects on myocardial infarct size (IS) reduction and enhancing nitric oxide synthase (NOS) expression. METHOD: Rats were randomized to nine groups: ATV-1 (1 mg/kg/d); ATV-10 (10 mg/kg/d); SL-0.7 (0.7 mg/kg); SL-1 (1 mg/kg); ATV-1 + SL-0.7; water alone (controls); 1400W (iNOS inhibitor; 1 mg/kg); ATV-10 + 1400W; and ATV-1 + SL-0.7 + 1400W. ATV was administered orally for 3 days. SL was administered intraperitoneally 18 h before surgery and 1400W intravenously 15 min before surgery. Rats either underwent 30 min ischemia-4 h reperfusion or the hearts were explanted for immunoblotting and enzyme activity tests without being exposed to ischemia. RESULTS: IS (% risk area, mean +/- SEM) was smaller in the ATV-10 (13 +/- 1%), SL-1 (11 +/- 2%), SL-0.7 (18 +/- 2%) and ATV-1 + SL-0.7 (9 +/- 1%) groups as compared with controls (34 +/- 3%; P < 0.001), whereas ATV-1 had no effect (29 +/- 2%). ATV-1 + SL-0.7 (9 +/- 1%) reduced IS more than SL-0.7 alone (p = 0.012). 1400W abrogated the protective effect of ATV-10 (35 +/- 3%) and ATV-1 + SL-0.7 (34 +/- 1%). SL-0.7 and ATV-10 increased phosphorylated endothelial (P-eNOS; 210 +/- 2.5% and 220 +/- 8%) and inducible (iNOS; 151 +/- 1% and 154 +/- 1%) NOS expression, whereas ATV-1 did not. These changes were significantly enhanced by ATV-1 + SL-0.7 (P-eNOS, 256 +/- 2%, iNOS 195 +/- 1%). SL-1 increased P-eNOS (311 +/- 22%) and iNOS (185 +/- 1%) concentrations. CONCLUSIONS: Combining low-dose ATV with SL augments the IS limiting effects through enhanced P-eNOS and iNOS expression.

Amidines↗

Statins are associated with lower risk of gastrointestinal bleeding in patients with unstable coronary syndromes: analysis of the Orbofiban in Patients with Unstable coronary Syndromes-Thrombolysis In Myocardial Infarction 16 (OPUS-TIMI 16) trial.

BACKGROUND: It has recently been shown that statins increase the myocardial content of prostaglandin (PG) I2 (prostacyclin) and PGE2. A systemic increase of PG production may protect the gastric mucosa and prevent gastrointestinal (GI) bleeding. We hypothesized that statins would lower the risk of GI bleeding associated with antiplatelet therapy in patients with acute coronary syndromes (ACS). METHODS: We retrospectively analyzed data on 10288 patients with ACS included in the OPUS-TIMI 16 trial and received aspirin and either the oral IIb/IIIa inhibitor orbofiban or placebo. RESULTS: Inhospital GI bleeding rate was significantly lower in patients who were receiving lipid-lowering drugs before admission compared with those who were not (0.2% vs 0.6%, P = .031). Throughout 10 months of follow-up, GI bleeding occurred in 1.8% of non-statin users compared with 1.0% of statin users (P = .001). Statin use was associated with less overall bleeding in both the orbofiban (1.4% vs 2.4%, P = .006) and the placebo groups (0.2% vs 0.8%, P = .047). Severe and major bleeding occurred less frequently with statin use (0.8% vs 1.5%, P = .001) in both the orbofiban (1.1% vs 2.0%, P = .006) and the placebo groups (0.1% vs 0.5%, P = .119). Logistic regression analysis showed that age > 65 years, orbofiban treatment, Killip class > 1, history of cerebrovascular disease, and calcium-channel blocker use were associated with higher risk of GI bleeding, whereas statin therapy was associated with a lower risk (odds ratio 0.68, 95% CI 0.45-1.04, P = .079). CONCLUSIONS: Statins may exert protective effect against GI bleeding in patients with ACS. Additional studies are warranted to explore this additional potential benefit of statins.

Acute Disease↗

Tolvaptan: a selective vasopressin type 2 receptor antagonist in congestive heart failure.

The neurohormone arginine vasopressin plays a significant role in the regulation of volume homeostasis, which is mediated via vasopressin type 2 (V2) receptors in the collecting tubules of the kidney. Diseases that are accompanied by abnormal volume homeostasis, including congestive heart failure and cirrhosis, are a frequent cause of hospital admissions and increasing healthcare costs. Recently, several nonpeptide V2 receptor antagonists have emerged as promising agents in the management of these conditions with the advantage of having no electrolyte abnormalities, neurohormonal activation or worsening renal insufficiency. Tolvaptan, a highly selective nonpeptide V2 receptor antagonist, has demonstrated an improvement in the volume status, osmotic balance and haemodynamic profile in preclinical and Phase II trials in patients with congestive heart failure and is currently undergoing testing in Phase III trials. This review discusses the evidence for the potential uses of tolvaptan, and its pharmacology and pharmacokinetics, particularly in congestive heart failure.

Antidiuretic Hormone Receptor Antagonists↗

Chronic pseudoaneurysm and coarctation of the aorta: a rare delayed complication of trauma.

We report an unusual case of pseudoaneurysm and coarctation of the descending thoracic aorta after trauma. The coarctation of aorta resulted in hypertension, severe left ventricular dysfunction, and symptoms of congestive heart failure. Surgical bypass resulted in control of blood pressure and improvement of heart failure symptoms. The mechanism of aortic injury leading to the development of this rare combination is discussed.

Accidents, Traffic↗

Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2.

We determined the effects of cyclooxygenase-1 (COX-1; SC-560), COX-2 (SC-58125), and inducible nitric oxide synthase (iNOS; 1400W) inhibitors on atorvastatin (ATV)-induced myocardial protection and whether iNOS mediates the ATV-induced increases in COX-2. Sprague-Dawley rats received 10 mg ATV.kg(-1).day(-1) added to drinking water or water alone for 3 days and received intravenous SC-58125, SC-560, 1400W, or vehicle alone. Anesthesia was induced with ketamine and xylazine and maintained with isoflurane. Fifteen minutes after intravenous injection rats underwent 30-min myocardial ischemia followed by 4-h reperfusion [infarct size (IS) protocol], or the hearts were explanted for biochemical analysis and immunoblotting. Left ventricular weight and area at risk (AR) were comparable among groups. ATV reduced IS to 12.7% (SD 3.1) of AR, a reduction of 64% vs. 35.1% (SD 7.6) in the sham-treated group (P < 0.001). SC-58125 and 1400W attenuated the protective effect without affecting IS in the non-ATV-treated rats. ATV increased calcium-independent NOS (iNOS) [11.9 (SD 0.8) vs. 3.9 (SD 0.1) x 1,000 counts/min; P < 0.001] and COX-2 [46.7 (SD 1.1) vs. 6.5 (SD 1.4) pg/ml of 6-keto-PGF(1alpha); P < 0.001] activity. Both SC-58125 and 1400W attenuated this increase. SC-58125 did not affect iNOS activity, whereas 1400W blocked iNOS activity. COX-2 was S-nitrosylated in ATV-treated but not sham-treated rats or rats pretreated with 1400W. COX-2 immunoprecipitated with iNOS but not with endothelial nitric oxide synthase. We conclude that ATV reduced IS by increasing the activity of iNOS and COX-2, iNOS is upstream to COX-2, and iNOS activates COX-2 by S-nitrosylation. These results are consistent with the hypothesis that preconditioning effects are mediated via PG.

Animals↗

Benefits, unresolved questions, and technical issues of cardiac resynchronization therapy for heart failure.

This review aims to provide a synthesis of the published evidence regarding the rationale and clinical benefits of cardiac resynchronization therapy (CRT) with implantable atrial-synchronized biventricular pacing (BVP) devices in patients with moderate to advanced heart failure and intra- and interventricular conduction delays. In addition, it addresses clinical and technical issues that have yet to be resolved, such as the selection of the most suitable candidates for CRT; the usefulness of combining BVP with automatic defibrillation backup; the value of CRT in patients with atrial fibrillation; the importance of alternative sites of pacing, such as the atrial septum and the right ventricular (RV) outflow tract; the harmful effects of the long-standing practice of producing an iatrogenic left bundle branch block by conventional RV pacing in patients receiving standard permanent pacemakers; the question of precisely where on the left ventricle optimal pacing is achieved; and the potential applications of CRT in patients with pediatric or congenital heart disease. Considering how major advances have been achieved since the first clinical application of CRT in 1994, one can be optimistic about the future of the electrotherapeutic management of heart failure.

Cardiac Pacing, Artificial↗

Vasopressin antagonism: a future treatment option in heart failure.

Arginine vasopressin plays an important role in volume homeostasis. Patients with heart failure have chronically elevated plasma vasopressin concentrations which may contribute to their clinical syndrome of fluid retention. Recently, a number of agents have been developed to antagonize the effects of vasopressin by targeting its V1a and V2 receptors, which are involved in vascular tone and free water regulation, respectively. Two vasopressin antagonists, in particular, tolvaptan and conivaptan, have shown promise in animal studies and small-scale human trials. The following is a review of current experimental and clinical studies using vasopressin antagonists and their potential role in the treatment of heart failure.

Antidiuretic Hormone Receptor Antagonists↗

Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury.

OBJECTIVES: Statins attenuate myocardial ischemic injury by activating nitric oxide synthase (NOS). It is unknown whether cyclooxygenase-2 (COX2), which mediates late ischemic preconditioning, also mediates statins-induced cardioprotection. We investigated the involvement of the prostaglandins and NOS in the cardioprotective effect of atorvastatin (ATV) in the rat. METHODS: Sprague-Dawley rats were randomized to a 3-day oral treatment with ATV 10 mg/kg, valdecoxib, a selective COX2 inhibitor (VAL) 3 mg/kg, ATV+VAL or water alone. Rats underwent 30-min myocardial ischemia followed by 4-h reperfusion. RESULTS: Infarct size was smaller in the ATV group (31.3+/-1.9%) than controls (44.5+/-3.1%; p=0.011) and VAL (44.5+/-3.1%; p=0.008). VAL attenuated the protective effect of ATV when administered together (40.2+/-2.5%). ATV pretreatment increased myocardial content of 6-keto-PGF(1alpha) (69.5+/-1.5 pg/mg) and PGE2 (57.9+/-0.6 pg/mg) compared with controls (16.2+/-0.2 and 42.1+/-2.0 pg/mg, respectively) and ATV+VAL (15.8+/-0.3 and 39.9+/-1.9 pg/mg, respectively). ATV increased myocardial content of cytosolic phospholipase A2 (cPLA2) (174.8+/-0.5%), COX2 (446.2+/-0.9%), PGI2 synthase (201.8+/-1.1%) and PGE2 synthase (122+/-0.7%), whereas ATV+VAL did not (123.0+/-7.9%, 93.8+/-8.5%, 103.0+/-1.6% and 99.0+/-0%, respectively). ATV did not change the myocardial content of eNOS and nNOS, but increased the concentration of phosphorylated eNOS (231.8+/-2.4%) and iNOS (154.5+/-1.2%). This effect was not blocked by coadministration of VAL (231.5+/-3.0% and 154.5+/-1.8%, respectively). CONCLUSIONS: Our results suggest that the prostaglandins are essential for mediating the myocardial protective effects of ATV and their production is downstream to eNOS phosphorylation and iNOS.

Animals↗