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3.
Catheter Cardiovasc Interv ; 91(5): E29-E42, 2018 04 01.
Article in English | MEDLINE | ID: mdl-23436313

ABSTRACT

Transcatheter aortic valve replacement (TAVR) with balloon-expandable Edwards-SAPIEN valve was superior to standard therapy in inoperable patients and noninferior to surgical aortic valve replacement in high surgical-risk, but operable patients, with severe symptomatic aortic stenosis in the randomized controlled PARTNER trial. Since the first case of TAVR with a balloon-expandable valve in 2002, several groups have reported their experience with balloon-expandable valves with high-procedural success. In the United States, the balloon-expandable Edwards-SAPIEN valve is the only transcatheter heart valve approved by the FDA for commercial use. Moreover, this is only in high-risk inoperable patients. Despite increasing experience with the TAVR procedure, it can be associated with complications, which can be technically challenging, even for an experienced operator. Complications associated with TAVR include vascular complications, valve malpositioning, regurgitation, embolization, coronary compromise, conduction abnormalities, stroke/transient ischemic attack, acute kidney injury, cardiac tamponade, and hemodynamic collapse. A thorough understanding of the procedure is essential for pre-emptive planning for procedural complications and early identification and management of complications are necessary for procedural success. We hereby review our experience of transfemoral TAVR with balloon-expandable valves, offer practical tips to maximize the likelihood of procedural success, describe pre-emptive strategies to prevent peri-procedural complications and bailout measures to manage them, should they occur. © 2018 Wiley Periodicals, Inc.


Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Balloon Valvuloplasty/adverse effects , Catheterization, Peripheral/adverse effects , Femoral Artery , Heart Valve Prosthesis , Postoperative Complications/prevention & control , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/instrumentation , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Clinical Decision-Making , Femoral Artery/diagnostic imaging , Humans , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Prosthesis Design , Punctures , Risk Factors , Severity of Illness Index , Transcatheter Aortic Valve Replacement/methods , Treatment Outcome
4.
Circ Cardiovasc Interv ; 10(11)2017 Nov.
Article in English | MEDLINE | ID: mdl-29138245

ABSTRACT

BACKGROUND: Diabetes mellitus (DM) adversely affects morbidity and mortality for cardiovascular diseases and procedures. Data evaluating the outcomes of transcatheter aortic valve replacement (TAVR) in diabetic patients are limited by small sample size and contradictory results. We aimed to establish the magnitude of risk and the incremental influence of insulin dependency by examining short- and long-term adverse outcomes according to DM status and therapy in the world's largest TAVR registry. METHODS AND RESULTS: We analyzed data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. In-hospital mortality, 30-day mortality, and 1-year mortality after TAVR in patients with and without DM were evaluated using multivariate modeling. Among 47 643 patients treated with TAVR from November 2011 through September 2015 at 394 US hospitals, there were 17 849 (37.5%) patients with DM. Overall, 6600 of the diabetic patients were insulin treated (IT). Thirty-day mortality was 5.0% in patients with DM (6.1% in IT DM and 4.4% in non-IT DM; P<0.001) versus 5.9% in patients without DM (P<0.001). Overall, 1-year mortality was 21.8% in patients with DM (24.8% in IT DM and 20.1% in non-IT DM; P<0.001) versus 21.2% in patients without DM (P=0.274). In a multivariable model, DM was associated with increased 1-year mortality (hazard ratio, 1.30; 95% confidence interval, 1.13-1.49; P<0.001). Subgroup multivariable analysis showed stronger mortality association in IT diabetics (hazard ratio, 1.57; 95% confidence interval, 1.28-1.91; P<0.001) than in non-IT diabetics (hazard ratio, 1.17; 95% confidence interval, 1.00-1.38; P=0.052). CONCLUSIONS: Our data establish the magnitude of short- and long-term risk conferred by DM and the incremental risk conferred by insulin dependency in the performance of TAVR. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01737528.


Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Transcatheter Aortic Valve Replacement , Aged , Aged, 80 and over , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/mortality , Chi-Square Distribution , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Female , Glomerular Filtration Rate , Hospital Mortality , Humans , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Kidney/physiopathology , Male , Multivariate Analysis , Odds Ratio , Proportional Hazards Models , Registries , Risk Factors , Time Factors , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/mortality , Treatment Outcome , United States/epidemiology
5.
J Tissue Eng ; 7: 2041731416646676, 2016.
Article in English | MEDLINE | ID: mdl-27213036

ABSTRACT

The lack of cell retention clearly represents a potentially serious limitation for therapeutic efficacy of stem cells. To enhance the efficacy, we developed a novel hydrogel that is thermosensitive and biodegradable and possesses desirable stiffness in a solid form. Immediately after induction of myocardial infarction of male rat, cardiac outgrowth cells embedded in hydrogel (HG) or saline (CO) were injected directly into the peri-infarct area. Left ventricular ejection fraction, cell retention rate, and a spectrum of biochemical markers were measured to evaluate the effect of the treatment. Left ventricular ejection fraction was significantly higher in the cell-injected groups (HG and CO) than in the control group at 1 week after treatment. This functional benefit was continued only in the HG group, accompanied with more retained cells. Furthermore, the expression of insulin-like growth factor-1 was significantly higher in the HG group with less progression of cell apoptosis.

6.
Article in English | MEDLINE | ID: mdl-25552490

ABSTRACT

BACKGROUND: Although computed tomography (CT) is commonly used for iliofemoral evaluation for transfemoral transcatheter aortic valve replacement, many centers worldwide use invasive angiography alone for this purpose. No study to date has evaluated the value of CT over angiography for the prediction of vascular complications. In addition, no data exist for the value of noncontrast CT. METHODS AND RESULTS: Of the 588 transcatheter aortic valve replacement patients, we reviewed 496 consecutive transfemoral cases. Vessel diameters were measured by CT or angiography. Sheath-related complication (SRC) was defined as an iliofemoral arterial injury not including a cannulation site. Receiver operating characteristic models were generated using sheath-to-iliofemoral artery ratios as a variable and SRC as an end point. In patients undergoing both contrast CT and angiography (n=283; 35 SRCs), contrast CT showed a greater predictive value than angiography by area under the curve P<0.001): 0.87 (95% confidence interval: 0.82-0.91) versus 0.72 (95% confidence interval: 0.66-0.77). In patients undergoing both noncontrast CT and angiography (n=103; 17 SRCs), there was no difference between noncontrast CT and angiography: 0.79 (95% confidence interval: 0.70-0.86) versus 0.73 (95% confidence interval: 0.63-0.81). Three-dimensional assessments of calcification and tortuosity provided limited additional value for SRC prediction. CONCLUSIONS: Contrast CT has a greater predictive value for post-transcatheter aortic valve replacement vascular complications than angiography. Because these complications increase mortality, an accurate assessment of the vasculature is a critical component of proper access selection.


Subject(s)
Aortic Valve Stenosis/therapy , Cardiac Catheterization/methods , Catheterization, Peripheral/methods , Femoral Artery/diagnostic imaging , Heart Valve Prosthesis Implantation/methods , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Aortic Valve Stenosis/diagnosis , Area Under Curve , Cardiac Catheterization/adverse effects , Cardiac Catheterization/instrumentation , Catheterization, Peripheral/adverse effects , Contrast Media , Female , Femoral Artery/injuries , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Humans , Logistic Models , Los Angeles , Male , Multivariate Analysis , Patient Selection , Predictive Value of Tests , ROC Curve , Reproducibility of Results , Severity of Illness Index , Treatment Outcome , Vascular System Injuries/etiology
8.
Eur Heart J ; 34(1): 68-75, 2013 Jan.
Article in English | MEDLINE | ID: mdl-21659438

ABSTRACT

AIMS: Cardiosphere-derived cells (CDCs) are in clinical development as a regenerative cell product which can be expanded ex vivo from patient cardiac biopsies. Cardiosphere-derived cells are clonogenic, exhibit multilineage differentiation, and exert functional benefits in preclinical models of heart failure. The origin of CDCs remains unclear: are these cells endogenous to the heart, or do they arise from cells that populate the heart via blood-borne seeding? METHODS AND RESULTS: Right ventricular endomyocardial biopsies were obtained from cardiac transplant recipients (n = 10, age 57 ± 15 years), and CDCs expanded from each biopsy. Donor-recipient mismatches were used to probe the origin of CDCs in three complementary ways. First, DNA analysis of short-tandem nucleotide repeats (STRs) was performed on genomic DNA from donor and recipient, then compared with the STR pattern of CDCs. Second, in two cases where the donor was male and the recipient female, CDCs were examined for the presence of X and Y chromosomes by fluorescence in situ hybridization. Finally, in two cases, quantitative PCR (qPCR) was performed for individual-specific polymorphisms of a major histocompatability locus to quantify the contribution of recipient cells to CDCs. In no case was recipient DNA detectable in the CDCs by STR analysis. In the two cases in which a female patient had received a male heart, all CDCs examined had an X and Y chromosome, similarly indicating exclusively donor origin. Likewise, qPCR on CDCs did not detect any recipient DNA. CONCLUSION: Cardiosphere-derived cells are of endogenous cardiac origin, with no detectable contribution from extra-cardiac seeding.


Subject(s)
Heart Ventricles/cytology , Myocardium/cytology , Myocytes, Cardiac/cytology , Stem Cells/cytology , Adult , Aged , Cell Differentiation/physiology , Cells, Cultured , DNA/analysis , Female , Heart Transplantation , Humans , In Situ Hybridization, Fluorescence , Male , Microsatellite Repeats , Middle Aged , Real-Time Polymerase Chain Reaction , Stem Cell Transplantation/methods , Young Adult
9.
Med Hypotheses ; 78(1): 166-70, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22075236

ABSTRACT

BACKGROUND/OBJECTIVES: ACC/AHA/SCAI recommendations include dual anti-platelet therapy (aspirin and clopidogrel) for 12 months after drug-eluting stent percutaneous coronary intervention (DES PCI). Numerous case reports have emerged of "very late stent thrombosis" (VLST) (>1 year post-DES-PCI) even 1-5 years after DES-PCI manifesting with myocardial infarction and death when clopidogrel therapy was interrupted or stopped. HYPOTHESIS: We hypothesize that a novel regimen of alternate day clopidogrel would provide a cost-effective strategy to prevent VLST taking into account the known facts about clopidogrel pharmacodynamics, stent endothelialization and stent thrombosis. We hypothesized that the degree of anti-platelet effect required to prevent VLST decreases with time as the stent endothelializes-that is the "therapeutic threshold" required to prevent VLST decreases with time. The anti-platelet effect of clopidogrel lasts for 5-7 days. Typically, stent thrombosis on interruption of clopidogrel (with bare metal stents within first 30 days) occurs after 3-4 days signifying recovery of enough platelet function to produce stent thrombosis--recovery of platelet inhibition beyond the therapeutic threshold. Since the therapeutic threshold required to prevent VLST in DES after 1 year is much lower, this degree of platelet inhibition can be conceivably achieved with just administering clopidogrel on alternate days. EMPIRICAL DATA: We studied efficacy and safety of regimen of daily aspirin 81 mg and alternate-day clopidogrel 75 mg beyond 12 months after PCI with DES for prevention of VLST by following 347 patients for occurrence of death, myocardial infarction (MI), VLST, target vessel revascularization (TVR) and bleeding. There were no occurrence of major bleeding, VLST events or death. CONCLUSIONS: Long term dual anti-platelet therapy with aspirin 81 mg daily and clopidogrel 75 mg every other day beyond 12 months after PCI with DES may be a safe and efficacious cost-saving strategy to prevent VLST.


Subject(s)
Coronary Thrombosis/prevention & control , Drug-Eluting Stents/adverse effects , Platelet Aggregation Inhibitors/pharmacology , Ticlopidine/analogs & derivatives , Aspirin/pharmacology , Clopidogrel , Cohort Studies , Coronary Thrombosis/etiology , Equipment Safety , Humans , Ticlopidine/pharmacology
10.
Catheter Cardiovasc Interv ; 79(6): 903-9, 2012 May 01.
Article in English | MEDLINE | ID: mdl-21805570

ABSTRACT

OBJECTIVE: Our aim was to compare the long-term outcomes between drug-eluting stents and bare-metal stents for saphenous vein graft stenosis. BACKGROUND: The ideal type of stent to treat saphenous vein graft stenosis has not been clearly established. Short-term randomized controlled trial results comparing drug-eluting stents with bare-metal stents for saphenous vein graft stenosis are conflicting, intermediate-term retrospective studies and meta-analyses at two years suggest no difference in outcomes, and there are no long term follow-up studies. The need for long term follow-up data has become emerged with concern over late stent thrombosis. METHODS: 246 saphenous vein graft patients undergoing stenting from August 2002-December 2008 were studied. Overall survival and event-free survival were compared by Kaplan-Meier method. Hazard ratios (HR) were calculated by Cox-proportional hazards models. RESULTS: We treated 133 patients with DES (median follow-up four years) and 113 patients with BMS (median follow-up four years) for SVG stenosis. Overall survival (77.0% ± 3.9% vs. 70.6% ± 4.6%, log-rank P = 0.60) and MACE-free survival (57.5% ± 4.6% vs. 56.8% ± 4.9, log-rank P = 0.70) were not significantly different between the DES and BMS groups. Although BMS was associated with increased risk of target lesion revascularization (TLR) (freedom from TLR 85.2% ± 3.5% vs. 90.0% ± 3.0%, HR 2.07, 95% CI 0.97-4.42, log-rank P = 0.05), there was no significant difference in the freedom from myocardial infarction (86.7% ± 3.3% vs. 88.7% ± 3.2%, log-rank P = 0.39) or target vessel revascularization (77.1% ± 4.2% vs. 76.1% ± 4.2%, log-rank P = 0.33) between the two groups. CONCLUSIONS: Although mortality is not statistically different between DES and BMS for SVG stenosis, BMS is associated with increased risk of revascularization, thus suggesting the superiority of DES over BMS in the long term.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Coronary Artery Bypass/adverse effects , Drug-Eluting Stents , Graft Occlusion, Vascular/therapy , Metals , Saphenous Vein/transplantation , Stents , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary/adverse effects , Angioplasty, Balloon, Coronary/mortality , Constriction, Pathologic , Coronary Angiography , Coronary Artery Bypass/mortality , Disease-Free Survival , Female , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/mortality , Humans , Kaplan-Meier Estimate , Los Angeles , Male , Predictive Value of Tests , Proportional Hazards Models , Prosthesis Design , Retrospective Studies , Risk Assessment , Risk Factors , Saphenous Vein/diagnostic imaging , Time Factors , Treatment Outcome
11.
Am J Cardiol ; 107(3): 360-6, 2011 Feb 01.
Article in English | MEDLINE | ID: mdl-21256999

ABSTRACT

The American College of Cardiology/American Heart Association recently updated recommendations for percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) disease from class III to II(b) according to the results of the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial. The SYNTAX score is an angiographic tool using solely the coronary anatomy. We studied the effect of co-morbidities (Parsonnet's score) on the ability of the SYNTAX score to predict long-term outcomes in patients with ULMCA disease treated by revascularization. A total of 328 patients underwent revascularization of ULMCA from April 2003 to February 2007. Of the 328 patients, 120 underwent PCI (median follow-up 973 days) and 208 underwent coronary artery bypass grafting (CABG) (median follow-up 1,298 days). The ability of the SYNTAX score to predict outcomes was assessed using the Cox proportional hazards model. The outcomes between the PCI and CABG groups were compared by propensity analysis. The median SYNTAX score was 26 in the PCI and 28 in the CABG group (p = 0.5). In the PCI group, greater quartiles were associated with worse survival (62.1% at SYNTAX score of ≥36 vs 82.4% at SYNTAX score of <36, p = 0.03) and all-cause mortality, myocardial infarction, cerebrovascular events, and target vessel revascularization-free (MACCE) survival (47.7%, SYNTAX score ≥20 vs 76.6%, SYNTAX score <20, p = 0.02). Using the Parsonnet score as a covariate, the SYNTAX score continued to be an independent predictor of MACCE and demonstrated a trend toward predicting mortality in the PCI group. In contrast, the SYNTAX score did not predict the outcomes for the CABG group. No difference was found in mortality between the PCI and CABG groups for ULMCA disease, regardless of coronary complexity; although greater SYNTAX scores were associated with increased MACCE rates with PCI compared to CABG. Both the coronary anatomy (SYNTAX score) and co-morbidities (Parsonnet's score) predicted long-term outcomes for PCI of ULMCA disease. In contrast, the SYNTAX score did not predict the outcomes after CABG. In conclusion, the ideal scoring system to guide an appropriate revascularization decision for ULMCA disease should take into account both the coronary anatomy and the co-morbidities.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Angiography , Coronary Disease/therapy , Aged , Comorbidity , Coronary Artery Bypass , Coronary Disease/mortality , Female , Humans , Male , Predictive Value of Tests , Propensity Score , Proportional Hazards Models , Treatment Outcome
12.
Am J Cardiol ; 106(8): 1075-80, 2010 Oct 15.
Article in English | MEDLINE | ID: mdl-20920641

ABSTRACT

A meta-analysis of published studies was conducted to evaluate the incidence, predictors, and clinical outcomes of stent fractures. Eight studies with 108 stent fractures in 5,321 patients were analyzed using the Bayesian method. Study end points included in-stent restenosis (ISR) and target lesion revascularization (TLR). The mean incidence of stent fracture per patient was 4.0% (95% confidence interval 0.4% to 16.3%). All cases, except 1, were reported with sirolimus-eluting stents. The incidence of stent fracture was 30.4% in the left anterior descending coronary artery, 10.9% in the left circumflex coronary artery, 56.4% in the right coronary artery, < 0.01% in the left main coronary artery, and 1.7% in saphenous vein grafts. The probability of stent fracture was significantly higher in the right coronary artery than in the left anterior descending and left circumflex lesions (p < 0.01). Left main stents were less likely to fracture compared to those in all other vessels (p < 0.01). The probability of stent fracture was significantly increased in overlapping stents (7.5% vs 2.1%, p = 0.01) and long stents (46 vs 32.5 mm, p < 0.01). Lesions with stent fractures had higher rates of ISR (38% vs 8.2%, p < 0.01) and TLR (17% vs 5.6%, p < 0.01). Conversely, the probability of stent fractures was higher in patients with ISR (12.8% vs 2.1%, p < 0.01) and TLR (8.8% vs 2.7%, p < 0.01). In conclusion, although not always associated with clinical sequelae, the probability of ISR and TLR is increased with stent fracture. Conversely, the probability of stent fractures is increased in lesions with ISR or TLR, thus raising the need for surveillance and management guidelines for at-risk patients.


Subject(s)
Coronary Restenosis/epidemiology , Coronary Restenosis/etiology , Myocardial Ischemia/surgery , Stents , Humans , Incidence , Prosthesis Failure , Risk Factors , United States/epidemiology
13.
Am J Cardiol ; 106(7): 994-8, 2010 Oct 01.
Article in English | MEDLINE | ID: mdl-20854963

ABSTRACT

Evidence from multiple large prospective studies suggests that a common polymorphism that encodes an arginine (Arg)-to-tryptophan substitution at position 719 in the KIF6 gene is associated with coronary heart disease (CHD) and reduction in coronary events from statin therapy. Carriers of the 719Arg allele were at greater risk for primary and secondary CHD events, and statin therapy significantly reduced coronary events in 719Arg carriers but not in noncarriers. The number needed to treat to prevent a single CHD event ranged from 10 to 20 for 719Arg carriers, compared to >80 for noncarriers in the Cholesterol and Recurrent Events (CARE) study, the West of Scotland Coronary Prevention Study (WOSCOPS), the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), and the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) study. In conclusion, assessment of 719Arg carrier status holds promise for stratification of coronary event risk and for selection of optimal therapy in primary and secondary CHD prevention.


Subject(s)
Coronary Disease/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Kinesins/genetics , Polymorphism, Genetic , Coronary Disease/drug therapy , Coronary Disease/prevention & control , Humans , Predictive Value of Tests , Primary Prevention , Risk Assessment , Risk Factors , Secondary Prevention
14.
J Am Coll Cardiol ; 56(8): 630-6, 2010 Aug 17.
Article in English | MEDLINE | ID: mdl-20705220

ABSTRACT

The new Adult Treatment Panel guidelines will be published in 2011. This paper suggests the consideration of major changes in the existing management guidelines for low-density lipoprotein cholesterol management based on 2 fundamental principles: return the low-density lipoprotein cholesterol level to the normal range and begin treatment closer to disease onset. These principles suggest the value of rethinking all 3 of the principal features of the Adult Treatment Panel III guidelines for low-density lipoprotein cholesterol management: the initiation criteria, the use of variable targets, and the level of the treatment target. Because the principal issue surrounding guideline change is likely to be uncertainty concerning cost and toxicity, the text of new guidelines would have to completely satisfy this concern by strong emphasis on a prudent conservative approach to implementation and would include both cautionary data and caveats concerning the tradeoffs between the potency, cost, and toxicity of statins. The proposed changes in the guidelines, if combined with effective implementation, would likely lead to the displacement of atherosclerotic disease as the nation's number 1 killer. This review provides a logical rationale and discusses the pros and cons for each of the proposed changes.


Subject(s)
Cholesterol, LDL/blood , Coronary Disease/prevention & control , Adult , Animals , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/prevention & control , Coronary Disease/blood , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Practice Guidelines as Topic , Reference Values , Risk Assessment , Risk Factors , Ultrasonography, Interventional
15.
Am J Cardiol ; 104(7): 972-7, 2009 Oct 01.
Article in English | MEDLINE | ID: mdl-19766766

ABSTRACT

The management strategy in asymptomatic patients with severe aortic stenosis (AS) is controversial. Aortic valve replacement has significant morbidity and mortality, while there is a risk for sudden cardiac death with conservative management. There is no consensus on the prognostic value of stress testing to stratify management. A pooled analysis of studies in patients with severe AS was performed to assess the prognostic value of stress testing for adverse events, including angina, dyspnea, acute heart failure, sudden death, and symptoms requiring aortic valve replacement. A search of published research was performed using the terms "stress test" and "asymptomatic aortic stenosis." A random-effects model was used to calculate pooled odds ratios and 95% confidence intervals. Data from 7 studies were included (491 patients with asymptomatic severe AS). None of the patients experienced any complications during or after stress testing. There were no sudden deaths in the patients with normal stress test results after 1 year of follow-up, while 5% with abnormal stress test results had sudden cardiac death. Overall, 52 of 253 patients (21%) with normal stress test results had adverse cardiac events, compared with 156 of 238 (66%) with abnormal stress test results (odds ratio 0.12, 95% confidence interval 0.07 to 0.21, p <0.001). In conclusion, stress testing in asymptomatic patients with severe AS is safe and identifies patients at risk for adverse cardiac events and sudden cardiac death. These data suggest that stress tests can be used for risk stratification and for deciding on the timing of aortic valve replacement in asymptomatic patients with severe AS.


Subject(s)
Aortic Valve Stenosis/diagnosis , Death, Sudden, Cardiac , Exercise Test , Aged , Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/surgery , Echocardiography, Doppler , Female , Heart Valve Prosthesis Implantation/methods , Humans , Male , Middle Aged , Prognosis , Randomized Controlled Trials as Topic , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Survival Analysis
17.
JACC Cardiovasc Interv ; 2(1): 1-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19463391

ABSTRACT

Meta-analyses of intracoronary autologous bone marrow cell infusion in patients with acute myocardial infarction establish the procedure as safe. Nonetheless, the typical small increase in ejection fraction is of uncertain clinical significance, with little if any evidence of myocardial regeneration. In this paper, we describe 3 new paradigms of myocardial preservation and regeneration that provide reasonable hope that the goal of myocardial rejuvenation can be achieved. The first paradigm is that substantial preservation of myocardium is possible even during the period of coronary occlusion and immediate reperfusion, before interventions aimed at myocardial regeneration. The factors that induce myocardial preservation may also create an environment more receptive to subsequent myocardial regeneration. The second paradigm is that the local environment may regulate the behavior of cells in the ischemic/infarct region. For instance, adult cells may be induced to re-enter the cell cycle and proliferate with appropriate environmental modification. The final paradigm is that autologous cardiac stem cells or induced pluripotent stem cells can create new myocytes and myocardium. Taken together, these new ideas, each still to be proven, suggest that the goal of regenerating functioning new myocardium can still be achieved.


Subject(s)
Myocardial Infarction/physiopathology , Myocardial Ischemia/physiopathology , Myocardium/pathology , Pluripotent Stem Cells/transplantation , Humans , Myocardial Infarction/complications , Myocardial Ischemia/complications , Myocardial Ischemia/therapy , Myocardial Reperfusion , Time Factors , Transplantation, Autologous
18.
JACC Cardiovasc Interv ; 1(3): 236-45, 2008 Jun.
Article in English | MEDLINE | ID: mdl-19463306

ABSTRACT

OBJECTIVES: The purpose of this study was to compare outcomes for drug-eluting stents (DES) and coronary artery bypass graft (CABG) surgery in patients with unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND: Expert guidelines recommend coronary artery bypass graft (CABG) surgery for the treatment of significant stenosis of the unprotected left main coronary artery (ULMCA) if the patient is eligible for CABG; however, treatment by percutaneous coronary intervention (PCI) is common. METHODS: Details of patients (n = 343, ages 69.9 +/- 11.9 years) undergoing coronary revascularization for ULMCA stenosis (April 2003 to January 2007) were recorded. A total of 223 patients were treated with CABG (mean [interquartile range]: follow-up 600 [226 to 977) days) and 120 by PCI (follow-up 362 [192 to 586) days). The hazard ratios (HRs) for death and major adverse cardiovascular and cerebrovascular events (MACCE) were calculated incorporating propensity score adjustment. Survival comparisons were conducted in propensity-matched subjects (n = 134), and in low- and high-risk subjects for CABG. RESULTS: Patients treated by PCI were more likely to be >or=75 years of age (49% vs. 33%; p = 0.005), and of greater surgical risk (Parsonnet score 17.2 +/- 11.2 vs. 13.0 +/- 9.3; p < 0.001) than patients treated by CABG. Overall, the propensity-adjusted HR for death was not statistically different (HR 1.93, 95% confidence interval [CI] 0.89 to 4.19, p = 0.10), but MACCE was greater in the PCI group (HR 1.83, 95% CI 1.01 to 3.32, p = 0.05). In propensity-matched individuals, neither survival nor MACCE-free survival were different. Survival was equivalent among low-risk candidates, but PCI had a tendency to inferior survival in high-risk candidates (Ellis category IV, log-rank p = 0.05). Interaction testing, however, failed to demonstrate a difference in outcomes of the 2 revascularization techniques as a function of baseline risk assessment. CONCLUSIONS: Overall, the propensity-adjusted risk of mortality for treatment of ULMCA disease does not differ between PCI- and CABG-treated groups. There appears to be sufficient equipoise that a randomized clinical trial to compare the techniques would not be ethically contraindicated.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Coronary Artery Bypass , Coronary Stenosis/therapy , Drug-Eluting Stents , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary/adverse effects , Angioplasty, Balloon, Coronary/mortality , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Cerebrovascular Disorders/etiology , Cerebrovascular Disorders/mortality , Coronary Angiography , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/mortality , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/mortality , Coronary Stenosis/surgery , Female , Humans , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Patient Selection , Proportional Hazards Models , Registries , Retrospective Studies , Risk Assessment , Time Factors , Treatment Outcome
19.
Catheter Cardiovasc Interv ; 70(1): 1-8, 2007 Jul 01.
Article in English | MEDLINE | ID: mdl-17580366

ABSTRACT

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.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Cardiovascular Agents/administration & dosage , Cardiovascular Diseases/prevention & control , Metals , Myocardial Infarction/therapy , Paclitaxel/administration & dosage , Sirolimus/administration & dosage , Stents , Aged , Angioplasty, Balloon, Coronary/adverse effects , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Clopidogrel , Coronary Angiography , Coronary Thrombosis/etiology , Coronary Thrombosis/prevention & control , Feasibility Studies , Female , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Male , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Platelet Aggregation Inhibitors/therapeutic use , Proportional Hazards Models , Prosthesis Design , Risk Assessment , Secondary Prevention , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use , Time Factors , Treatment Outcome
20.
Am J Cardiol ; 99(5): 732-8, 2007 Mar 01.
Article in English | MEDLINE | ID: mdl-17317382

ABSTRACT

Inflammatory cytokines have a central role in atherogenesis and plaque rupture. These mediators, including tumor necrosis factor, interleukins, and matrix metalloproteinases and transforming growth factor-beta are also prominent in other chronic progressive diseases characterized by cell apoptosis and tissue fibrosis. This review extends the inflammation hypothesis to critical analysis of studies to bearing on the role of inflammation in chronic conditions that commonly accompany coronary disease. Because statins inhibit the expression of inflammatory mediators, the review then analyzes the laboratory and clinical data that may justify trials of statins in nonatherosclerotic disease. In conclusion, despite far different clinical presentations, chronic progressive diseases characterized by apoptosis and fibrosis have persistence of inflammatory cytokines as a final common pathway, and thus may benefit from the pleiotropic effects of statin therapy.


Subject(s)
Cytokines/physiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Inflammation/etiology , Chronic Disease , Cytokines/drug effects , Humans , Inflammation/pathology , Inflammation/physiopathology
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