Cardioprotective effect of high-dose intragraft adenosine infusion on microvascular function and prevention of no-reflow during saphenous vein grafts intervention.

BACKGROUND: Despite the use of embolic protection devices, no-reflow can still occur during saphenous vein grafts (SVGs) intervention. High-dose intracoronary adenosine infusion preconditions the myocardium, improves coronary flow, and prevents no-reflow. The role of high-dose intragraft adenosine infusion on protection of microvascular function and prevention of no-reflow has not been investigated OBJECTIVES: We investigated the cardioprotective effect of high-dose intragraft adenosine infusion, compared with placebo, on microvascular function and prevention of no-reflow during SVGs intervention. METHODS: We randomized 22 patients with SVGs stenoses to receive either a 10-min intragraft adenosine infusion (200 µg/min; total dose = 2,000 µg) or normal saline prior to stenting. Average peak velocity (APV), coronary flow velocity reserve (CVR), thrombolysis in myocardial infarction (TIMI) frame count (TFC), TIMI myocardial perfusion grade (TMPG), and the rate of no-reflow were compared between the two groups before adenosine or saline infusions and after stenting RESULTS: After stenting, hyperemic APV, CVR, and TMPG were significantly higher in the adenosine-treated group than in the control group (60 ± 18 vs. 35 ± 10 cm/sec; 2.6 ± 0.54 vs. 1.8 ± 0.47; and 2.8 ± 0.90 vs. 2.1 ± 0.80, respectively; P < 0.05. TFC was significantly lower in the adenosine-treated group than in the control group (14 ± 3.0 vs. 26 ± 13; P < 0.05). In the control group, four patients (36%) developed no-reflow compared to none in the adenosine-treated patient; P < 0.05 CONCLUSIONS: This study provides the first evidence that high-dose intragraft adenosine infusion compared with placebo protects microvascular function and prevents no-reflow during SVGs intervention.

Coronary and intracerebral arterial aneurysms in a young adult with acute coronary syndrome.

A 21-year-old man with no known medical history presented with substernal chest pain. Serial 12-lead electrocardiography showed dynamic ST-segment elevations in the anterolateral leads. Emergent coronary angiography revealed diffuse coronary aneurysmal disease and thrombotic occlusion of the left anterior descending coronary artery. The patient underwent urgent coronary artery bypass grafting. Subsequent imaging showed intracerebral aneurysms that involved his right and left middle cerebral arteries. The incidence, multiple causes, and proposed mechanisms of coronary artery aneurysmal formation are discussed, as is the rare association of these lesions with extracardiac arterial aneurysms.This association between coronary and extracardiac aneurysms is a phenomenon that warrants further study to determine its prevalence and possible causes. Findings could influence recommendations for further screening of patients diagnosed with coronary aneurysmal disease.

Physiological assessment of renal artery stenosis: comparisons of resting with hyperemic renal pressure measurements.

OBJECTIVES: We compared resting and hyperemic pressure gradients induced by intrarenal papaverine for the assessment of renal artery stenosis (RAS). We also investigated the incidence of the QT interval prolongation and ventricular arrhythmias. BACKGROUND: In the coronary circulation, maximal hyperemia is essential in determining the significance of a stenosis. In the renal circulation, the role of maximal hyperemia for the assessment of RAS has not been established. METHODS: In 55 patients with RAS (67 RAS), resting P(d)/P(a) ratio (the ratio between distal renal pressure to the aortic pressure), renal fractional flow reserve (FFR), and resting and hyperemic systolic gradients (RSG and HSG, respectively) were measured with a pressure guidewire. In a subset of 16 patients, renal vein renin activity (RVRA) was measured. RESULTS: HSG was significantly greater than RSG (20 ± 14 mm Hg vs. 9.0 ± 13 mm Hg, respectively; P < 0.001). Renal FFR was significantly lower than baseline P(d)/P(a) ratio (0.91 ± 0.06 vs. 0.94 ± 0.06 vs. respectively; P < 0.001). RVRA increased from 50 ± 66% at rest to 122 ± 112% at hyperemia, P < 0.01. At HSG of 21 mm Hg or renal FFR of 0.90, RVRA increased markedly (120%), but RVRA increased modestly (18%) when RSG was 16 mm Hg or resting P(d)/P(a) ratio was 0.93. The corrected QT intervals at baseline vs. hyperemia were not significantly different (433 ± 26 vs. 436 ± 25 msec, respectively; P = NS); no episodes of ventricular arrhythmias were noted. CONCLUSIONS: Renin production, an index of renal ischemia, was markedly greater at hyperemia than at rest, suggesting that RAS, with either an HSG of 21 mm Hg or a renal FFR of 0.90, can be considered a hemodynamically significant stenosis. Intrarenal papaverine neither prolonged the QT interval nor induced ventricular arrhythmias and the safety of which will need to be corroborated in a large study. © 2010 Wiley-Liss, Inc.

Echocardiographic predictors of pulmonary hypertension in patients with severe aortic stenosis.

BACKGROUND: Pulmonary hypertension complicating severe aortic stenosis increases morbidity and mortality. Causes and mechanisms of this are unclear. METHODS: This is a retrospective observational study of 626 patients with severe aortic stenosis who had measurable pulmonary arterial pressure by Doppler echocardiography. Clinical, echocardiographic and pharmacological data were related to the presence of pulmonary hypertension. RESULTS: Of the 626 patients, 119 (19%) had severe pulmonary hypertension defined as pulmonary artery systolic pressure > or =60 mmHg. Patients with severe pulmonary hypertension had a smaller aortic valve area (P < 0.0001), a lower left ventricular ejection fraction (P < 0.0001), a higher mitral E/A velocity ratio (P < 0.0001) indicating a higher filling pressure and a higher prevalence of 3 or 4+ mitral regurgitation (P < 0.001). They were less likely to be on a beta blocker (P = 0.05) or a statin (P = 0.02). Smaller aortic valve area, left ventricular dysfunction, mitral regurgitation and lack of statin use were independent predictors of severe pulmonary hypertension. CONCLUSIONS: Severity of aortic stenosis, left ventricular dysfunction, and mitral regurgitation are risk factors for the genesis of pulmonary hypertension and statins may potentially be protective in patients with severe aortic stenosis.

Comparison of drug-eluting stents with bare metal stents in unselected patients with acute myocardial infarction.

OBJECTIVES: The aim of this study was to compare the procedural characteristics and outcomes of patients with acute myocardial infarction treated with drug-eluting stents (DES) vs. bare metal stents (BMS). BACKGROUND: DES have been shown to reduce the incidence of restenosis and target vessel revascularization (TVR) in clinical randomized studies when compared with BMS in patients undergoing elective percutaneous intervention. Limited data are available with the use of DES in patients with acute ST-segment elevation myocardial infarction. METHODS: Two hundred and sixty-one consecutive patients who presented with myocardial infarction between 7/2001 and 8/2005 were studied. The procedural characteristics, 30-day and 12-month outcomes of 131 patients treated with DES were compared with 130 patients treated with BMS. RESULTS: At 12-months follow-up DES therapy was associated with a substantial decrease in major adverse cardiovascular events (MACE) (HR 0.33; P =0.002), TVR (HR 0.19; P =0.002), and recurrent myocardial infarction (HR 0.23; P =0.051) vs. BMS therapy. Coronary interventions utilizing DES were characterized by a marked increase in the number of stent per target vessel (DES: 1.9 +/- 0.9 vs. BMS: 1.38 +/- 0.6, P < 0.0001), treatment of bifurcation (DES: 21% vs. BMS: 5%, P =0.0004), and multivessel intervention (DES: 22% vs. BMS: 8%, P =0.003). CONCLUSION: The routine use of DES in acute myocardial infarction is associated with reduced rates of MACE at 12 months vs BMS, despite a higher rate of complex procedures in the DES treated patients. In addition to its anti-restenosis effect, the improved outcome of patients treated with DES may be linked to a more complete revascularization in association with prolonged clopidogrel therapy.

Aortic valve replacement improves survival in severe aortic stenosis associated with severe pulmonary hypertension.

BACKGROUND: Severe pulmonary arterial hypertension in patients with severe aortic stenosis (AS) carries a poor prognosis. There are limited data on the effect of aortic valve replacement (AVR) in these patients. METHODS: Our echocardiographic database between 1993 and 2003 was searched for patients with severe AS defined as a Doppler estimated aortic valve area of 0.8 cm2 or less and severe pulmonary hypertension defined as a pulmonary arterial systolic pressure 60 mm Hg or greater. Of the 740 patients with severe AS, 119 (16%) had severe pulmonary hypertension forming the study cohort. The AVR was performed in 36 (30%) of these patients. Survival of patients with and without AVR were compared and adjusted for comorbidities and group differences using the Cox regression model. RESULTS: Characteristics of patients with severe pulmonary hypertension; age 75 +/- 13 years, 39% women, left ventricular ejection fraction 41 +/- 20%. Patients who underwent AVR had a significantly higher five-year survival of 65% compared with 20% for those treated medically (p < 0.0001). The relative mortality risk associated with AVR was 0.28 (95% confidence interval 0.22 to 0.36) and was independent of age, gender, ejection fraction, diabetes, coronary disease, serum creatinine level, and concomitant medical therapy such as beta blockers, angiotensin converting inhibitors, and statins. The benefit of AVR was further supported by sensitivity and propensity score analyses. Patients on conservative therapy had a 30-day mortality of 30% and a one-year mortality of 70%. CONCLUSIONS: Aortic valve replacement in patients with severe pulmonary hypertension secondary to severe AS is associated with a huge survival benefit. Medical therapy alone carries a dismal prognosis and AVR should be considered urgently in severe AS patients with severe pulmonary hypertension.

Comparison of bypass surgery with drug-eluting stents for diabetic patients with multivessel disease.

BACKGROUND: This retrospective study of prospectively collected data compared coronary artery bypass graft (CABG) surgery to drug-eluting stenting (DES) in diabetic patients with multivessel coronary artery disease (CAD). Prior randomized trials and clinical studies have suggested that CABG may be the preferred revascularization strategy in diabetic patients with multivessel CAD. Data are limited regarding the impact of DES vs. CABG on clinical outcomes. METHODS: We included 205 consecutive diabetic patients who underwent either CABG (n=103) or DES (n=102). The primary clinical end points were freedom from major adverse cardiac events (MACE) at 30 days and 1 year. RESULTS: Baseline characteristics were similar between both groups. At 1 year, the mortality rate was similar in the CABG and DES group (8% vs. 10%, p=0.6) but the MACE rate was lower in the CABG group (12% vs. 27%, p=0.006) due to less repeat revascularization with CABG (3% vs. 20%, p<0.001). Stroke occurred only in the CABG group (4% vs. 0%, p=0.04). Angiographically-documented stent thrombosis after DES occurred in 3%. Presentation with acute myocardial infarction (hazard ratio [HR], 2.26, 95% CI, 1.13 to 4.55) and DES (HR, 2.4, 95% CI, 1.23 to 4.77) were positive independent predictors, whereas therapy with a statin was a negative independent predictor of MACE (HR, 0.40, 95% CI, 0.21 to 0.76). CONCLUSIONS: Bypass surgery was associated with less MACE primarily due to the higher repeat revascularization rate with DES and is therefore superior to DES despite more extensive CAD in CABG patients.

Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis.

BACKGROUND: Severe aortic stenosis (AS) is a surgically correctable condition. However, aortic valve replacement (AVR) is not offered to many patients with severe AS for various reasons. We investigated the profile and survival patterns of patients with severe AS who did not have AVR. METHODS: Our echocardiographic database was screened for patients with severe AS, defined as a Doppler estimated aortic valve area of 0.8 cm2 or less between 1993 and 2003. Seven hundred and forty patients with severe AS were identified, of whom 453 patients had no AVR through the follow-up period, forming the study cohort. These patients were comprehensively characterized by obtaining clinical, pharmacologic, and surgical data through a comprehensive chart review and extracting survival data from the National Death Index. RESULTS: Patient characteristics were as follows: age 75 +/- 13 years, 48% male, left ventricular (LV) ejection fraction 52 +/- 21%, coronary artery disease in 34%, hypertension in 35%, serum creatinine level greater than 2 mg/dL in 11%, and diabetes mellitus in 14%. The survival at 1 year, 5 years, and 10 years was 62%, 32%, and 18%, respectively. The univariate predictors of reduced survival were advanced age, low LV ejection fraction, heart failure, elevated serum creatinine level, severe mitral regurgitation, and pulmonary hypertension; and the independent predictors were advanced age, low LV ejection fraction, heart failure, elevated serum creatinine level, and systemic hypertension. Concomitant pharmacotherapy had no impact on survival. CONCLUSIONS: Conservatively treated patients with severe AS have a grave prognosis, and it is worse in the presence of advanced age, LV dysfunction, heart failure, and renal failure.

Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement.

BACKGROUND: Patients with asymptomatic severe aortic stenosis (AS) are reported to have a benign prognosis and hence the American College of Cardiology/American Heart Association guidelines do not recommend aortic valve replacement (AVR) for patients with isolated asymptomatic severe AS. However, symptoms are subjective and would depend upon patient's life style. We examined the natural and unnatural history of initially asymptomatic patients with severe AS. METHODS: A search of our echocardiographic database between 1993 and 2003 yielded 740 patients with severe AS defined as aortic valve area 0.8 cm2 or less. Thorough chart reviews were conducted to collect clinical and pharmacologic data. Of these, 338 patients were asymptomatic at the initial encounter forming the study cohort. RESULTS: Patient characteristics were the following: age 71 +/- 15 years, males 51%, aortic valve area 0.72 +/- 0.17 cm2, left ventricular ejection fraction 0.59 +/- 0.17. Ninety-nine (29%) patients had AVR during a mean follow-up of 3.5 years. Survival at 1, 2, and 5 years in the nonoperated patients were 67%, 56%, and 38%, respectively, compared with 94%, 93%, and 90% in those who underwent AVR (p < 0.0001). The Cox regression model was used to adjust for the effect of 18 clinical, echocardiographic, and pharmacologic variables on survival. The adjusted hazard ratio for death with AVR was 0.17 (95% confidence interval [CI] 0.10 to 0.29). In the nonoperated group, renal insufficiency (risk ratio [RR] 3.1, 95% CI 1.5 to 6.6), beta blocker use (RR 0.52, 95% CI 0.31 to 0.88), statin use (RR 0.52, 95% CI 0.27 to 0.99), age (per year RR 1.03, 95% CI 1.02 to 1.05), and left ventricular ejection fraction (per % RR 0.99, 95% CI 0.98 to 1.00) were found to be the independent predictors of mortality. The benefit of AVR was further supported by sensitivity and propensity score analyses. CONCLUSIONS: Our observational data indicate that the natural history of asymptomatic AS is not benign and that survival is dramatically improved by AVR. Survival of the asymptomatic unoperated or nonoperable patients may potentially be improved by the use of beta blockers and statins.

Survival in elderly patients with severe aortic stenosis is dramatically improved by aortic valve replacement: Results from a cohort of 277 patients aged > or =80 years.

BACKGROUND: Calcific aortic stenosis (AS) is a disease of the elderly. However, there is reluctance to offer aortic valve replacement (AVR) for elderly patients with severe AS. We investigated if AVR confers a survival benefit in elderly patients with severe AS. METHODS: We screened our echocardiographic database from 1993 to 2003 for patients with severe AS (AV area < or = 0.8 cm2) and age > or =80 years. Two hundred and seventy seven patients were identified. Complete chart reviews were performed for clinical data. Mortality data were obtained from National Death Index. Survival curves of patients who underwent AVR during the follow-up period were compared with those managed nonsurgically. RESULTS: Patient characteristics were as follows: age 85+/-4 years, 53% male, AV area 0.68+/-0.16 cm2, EF 52+/-20%, CAD 47%, diabetes 17%. Over a mean follow-up of 2.5 years, 55 (20%) had AVR and there were 175 deaths. One-year, 2-year and 5-year survival rates among patients with AVR were 87, 78 and 68% respectively, compared with 52, 40 and 22%, respectively, in those who had no AVR (p < 0.0001). Hazard ratio for death with AVR adjusted for 19 covariates including age, EF, gender, comorbidities and pharmacotherapy was 0.38 (95% CI 0.26-0.66, p < 0.0001). CONCLUSION: Prognosis of medically managed severe calcific AS in the elderly patients is dismal. AVR appears to improve survival of these patients and should be strongly considered in the absence of other major comorbidities.

Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease.

OBJECTIVES: This study evaluated the clinical outcomes of consecutive, selected patients treated with coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for unprotected left main coronary artery (ULMCA) disease. BACKGROUND: Although recent data suggest that PCI with DES provides better clinical outcomes compared to bare-metal stenting for ULMCA disease, there is a paucity of data comparing PCI with DES to CABG. METHODS: Since April 2003, when DES first became available at our institution, 123 patients underwent CABG, and 50 patients underwent PCI with DES for ULMCA disease. RESULTS: High-risk patients (Parsonnet score >15) comprised 46% of the CABG group and 64% of the PCI group (p = 0.04). The 30-day major adverse cardiac and cerebrovascular event (MACCE) rate for CABG and PCI was 17% and 2% (p < 0.01), respectively. The mean follow-up was 6.7 +/- 6.2 months in the CABG group and 5.6 +/- 3.9 months in the PCI group (p = 0.26). The estimated MACCE-free survival at six months and one year was 83% and 75% in the CABG group versus 89% and 83% in the PCI group (p = 0.20). By multivariable Cox regression, Parsonnet score, diabetes, and CABG were independent predictors of MACCE. CONCLUSIONS: Despite a higher percentage of high-risk patients, PCI with DES for ULMCA disease was not associated with an increase in immediate or medium-term complications compared with CABG. Our data suggest that a randomized comparison between the two revascularization strategies for ULMCA may be warranted.