Searched for: in-biosketch:true
person:hochmj03
Incidence and outcomes associated with early heart failure pharmacotherapy in patients with ongoing cardiogenic shock
van Diepen, Sean; Reynolds, Harmony R; Stebbins, Amanda; Lopes, Renato D; Dzavik, Vladimir; Ruzyllo, Witold; Geppert, Alexander; Widimsky, Petr; Ohman, E Magnus; Parrillo, Joseph E; Dauerman, Harold L; Baran, David A; Hochman, Judith S; Alexander, John H
OBJECTIVES: Guidelines recommend beta-blockers and renin-angiotensin-aldosterone system blockers to improve long-term survival in hemodynamically stable myocardial infarction patients with a reduced left ventricular ejection fraction. The prevalence and outcomes associated with beta and renin-angiotensin-aldosterone system blocker therapy in patients with ongoing cardiogenic shock is unknown. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: In patients with cardiogenic shock lasting more than 24 hours enrolled in Tilarginine Acetate Injection in a Randomized International Study in Unstable Myocardial Infarction Patients With Cardiogenic Shock, we compared 30-day mortality in patients who received beta or renin-angiotensin-aldosterone system blockers (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonists) within 24 hours of randomization with those who did not. INTERVENTIONS: None. PATIENTS: The final study population included 240 patients. A total of 66 patients (27.5%) had either beta blocker or renin-angiotensin-aldosterone system blocker administered within the first 24 hours after the diagnosis of cardiogenic shock. beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aldosterone antagonists were prescribed in 18.8%, 10.6%, and 5.0% of patients, respectively. MEASUREMENTS AND MAIN RESULTS: The observed 30-day mortality among patients was higher in patients who received beta or renin-angiotensin-aldosterone system blockers prior to cardiogenic shock resolution (27.3% vs 16.9%; adjusted hazard ratio, 2.36; 95% CI, 1.06-5.23; p = 0.035). Compared with patients not given beta or renin-angiotensin-aldosterone system blockers, the 30-day mortality was higher among patients treated only with beta-blockers (33.3% vs 16.9%, p = 0.017) but not among those only treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (18.2% vs 16.9%, p = 1.000). CONCLUSIONS: The administration of beta or renin-angiotensin-aldosterone system blockers is common in North America and Europe in patients with myocardial infarction and cardiogenic shock prior to cardiogenic shock resolution. This therapeutic practice was independently associated with higher 30-day mortality, although a statistically significant difference was only observed in the subgroup of patients administered beta-blockers.
PMID: 23982033
ISSN: 0090-3493
CID: 759512
Mechanical circulatory support in cardiogenic shock
Werdan, Karl; Gielen, Stephan; Ebelt, Henning; Hochman, Judith S
Despite advances in coronary revascularization and widespread use of primary percutaneous interventions, cardiogenic shock complicating an acute ST-elevation myocardial infarction (CSMI) remains a clinical challenge with high mortality rates. Conservative management with catecholamines is associated with serious limitations, including arrhythmias, increased myocardial oxygen consumption, and inadequate circulatory support. Clinicians have therefore turned to mechanical means of circulatory support. Circulatory assist systems for CSMI can be distinguished by the method of placement (i.e. percutaneous vs. surgical), the type of circulatory support (i.e. left ventricular, right ventricular, or biventricular pressure and/or volume unloading), and whether they are combined with extracorporal membrane oxygenation (ECMO). The percutaneous assist systems most commonly used in CSMI are the intra-aortic balloon pump (IABP), venoarterial ECMO, the Impella pump, and the TandemHeart. Decades of clinical studies and experience demonstrated haemodynamic improvement, including elevation of diastolic perfusion pressure and cardiac output. Recently, the large randomized IABP-Shock II Trial did not show a significant reduction in 30-day mortality in CSMI with IABP insertion. There are no randomized study data available for ECMO use in CSMI. Both the Impella pump and the TandemHeart did not reduce 30-day mortality when compared with IABP in small randomized controlled trials (RCTs). In conclusion, despite the need for effective mechanical circulatory support in CSMI, current devices, as tested, have not been demonstrated to improve short- or long-term survival rates. RCTs testing the optimal timing of device therapy and optimal device design are needed to improve outcomes in CSMI.
PMID: 24014384
ISSN: 0195-668x
CID: 815642
Evolution of Differences in Women and Men With Non-ST-Segment Elevation Acute Coronary Syndromes: Insights From Clinical Trials Over 15 Years [Meeting Abstract]
Halim, Sharif; Yang, Qinghong; Schulte, Phillip; Hochman, Judith; Melloni, Chiara; Mahaffey, Kenneth W; Moliterno, David J; Harrington, Robert A; White, Harvey D; Armstrong, Paul W; Ohman, EMagnus; Van de Werf, Frans; Giugliano, Robert P; Newby, LKristin
ISI:000332162905212
ISSN: 1524-4539
CID: 1015502
Prognostic implications of left ventricular end-diastolic pressure during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Findings from the Assessment of Pexelizumab in Acute Myocardial Infarction study
Bagai, Akshay; Armstrong, Paul W; Stebbins, Amanda; Mahaffey, Kenneth W; Hochman, Judith S; Weaver, W Douglas; Patel, Manesh R; Granger, Christopher B; Lopes, Renato D
BACKGROUND: Left ventricular end-diastolic pressure (LVEDP) is frequently measured during primary percutaneous coronary intervention (PCI). However, little is known of this measurement's utility in predicting outcomes or informing treatment decisions. We sought to determine the prognostic value of LVEDP measured during primary PCI for ST-segment elevation myocardial infarction (STEMI). METHODS: We studied 1,909 (33.2%) of 5,745 STEMI patients in whom LVEDP was measured during primary PCI in the APEX-AMI trial. Cox regression analysis was used to evaluate whether LVEDP was an independent predictor of mortality and the composite of death, cardiogenic shock, or congestive heart failure (CHF) at 90 days. RESULTS: The median (25th, 75th percentiles) LVEDP level was 22 mm Hg (16, 29); compared with patients with LVEDP =22 mm Hg, those with LVEDP >22 mm Hg had higher rates of CHF (7.3% vs 3.1%, P < .001), cardiogenic shock (4.6% vs 1.7%, P < .001), and death (4.1% vs 2.2%, P = .014) at 90 days. After multivariable adjustment, LVEDP was associated with increased risk of mortality through 90 days (adjusted hazard ratio 1.22, 95% CI 1.02-1.46, per 5-mmHg increase, P = .044) and the composite of death, cardiogenic shock, or CHF within the first 2 days (adjusted hazard ratio 1.40, 95% CI 1.23-1.59, per 5-mm Hg increase, P < .001), but not from day 3 to 90 (P = .25). CONCLUSIONS: Left ventricular end-diastolic pressure measured during primary PCI for STEMI is an independent predictor of inhospital and longer term cardiovascular outcomes. Measuring LVEDP may be useful to stratify patient risk and guide postinfarct treatment.
PMID: 24176448
ISSN: 0002-8703
CID: 656802
Physical activity in patients with stable coronary heart disease: an international perspective
Stewart, Ralph; Held, Claes; Brown, Rebekkah; Vedin, Ola; Hagstrom, Emil; Lonn, Eva; Armstrong, Paul; Granger, Christopher B; Hochman, Judith; Davies, Richard; Soffer, Joseph; Wallentin, Lars; White, Harvey
AIMS: Despite the known benefits of regular exercise, the reasons why many coronary heart disease (CHD) patients engage in little physical activity are not well understood. This study identifies factors associated with low activity levels in individuals with chronic CHD participating in the STABILITY study, a global clinical outcomes trial evaluating the lipoprotein phospholipaseA2 inhibitor darapladib. METHODS AND RESULTS: Prior to randomization, 15 486 (97.8%) participants from 39 countries completed a lifestyle questionnaire. Total physical activity was estimated from individual subject self-reports of hours spend each week on mild, moderate, and vigorous exercise, corresponding approximately to 2, 4, and 8 METS, respectively. Multivariate logistic regression evaluated clinical and demographic variables for the lowest compared with higher overall exercise levels, and for individuals who decreased rather than maintained or increased activity since diagnosis of CHD. The least active 5280 subjects (34%) reported exercise of = 24 MET.h/week. A total of 7191 subjects (46%) reported less exercise compared with before diagnosis of CHD. The majority of participants were either 'not limited' or 'limited a little' walking 100 m (84%), climbing one flight of stairs (82%), or walking 1 km/1/2; mile (68%), and <10% were limited 'a lot' by dyspnoea or angina. Variables independently associated with both low physical activity and decreasing exercise after diagnosis of CHD included more co-morbid conditions, poorer general health, fewer years of education, race, and country (P < 0.001 for all). CONCLUSION: In this international study, low physical activity was only partly explained by cardiovascular symptoms. Potentially modifiable societal and health system factors are important determinants of physical inactivity in patients with chronic CHD.
PMCID:3819591
PMID: 24014220
ISSN: 0195-668x
CID: 687772
Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study
Kruk, Mariusz; Menon, Venu; Kadziela, Jacek; Sadowski, Zygmunt; Ruzyllo, Witold; Janas, Jadwiga; Roik, Marek; Opolski, Grzegorz; Zmudka, Krzysztof; Czunko, Piotr; Kurowski, Michal; Busz-Papiez, Benita; Zinka, Elzbieta; Jablonski, Wojciech; Jaworska, Krystyna; Raczynska, Anna; Skonieczny, Grzegorz; Forman, Sandra; Li, Daner; Hochman, Judith
BACKGROUND: The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis. METHODS: Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 +/- 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3. RESULTS: Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted. CONCLUSIONS: There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers' release.
PMCID:3871016
PMID: 24156746
ISSN: 1471-2261
CID: 759592
Prognostic relevance of baseline pro- and anti-inflammatory markers in STEMI: An APEX AMI substudy
van Diepen, Sean; Newby, L Kristin; Lopes, Renato D; Stebbins, Amanda; Hasselblad, Vic; James, Stefan; Roe, Matthew T; Ezekowitz, Justin A; Moliterno, David J; Neumann, Franz-Josef; Reist, Craig; Mahaffey, Kenneth W; Hochman, Judith S; Hamm, Christian W; Armstrong, Paul W; Granger, Christopher B; Theroux, Pierre
BACKGROUND: Plaque rupture, acute ischemia, and necrosis in acute coronary syndromes are accompanied by concurrent pro- and anti-inflammatory cascades. Whether STEMI clinical prediction models can be improved with the addition of baseline inflammatory biomarkers remains unknown. METHODS: In an APEX-AMI trial substudy, 772 patients had a panel of 9 inflammatory serum biomarkers, high sensitivity C reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline after randomization. Baseline biomarkers were incorporated into a clinical prediction model for a composite of 90-day death, shock, or heart failure. Incremental prognostic value was assessed using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). RESULTS: Individually, several biomarkers were independent predictors of clinical outcome: hsCRP (hazard ratio [HR] 1.12; 95% confidence interval [CI], 1.03-1.21; p=0.007, per doubling), NT-proBNP (HR 1.14; 95% CI, 1.06-1.23; p<0.001, per doubling), interleukin (IL)-6 (HR 1.26; 95% CI, 1.12-1.41;p<0.001, per doubling), and inducible protein-10 (IP-10) (HR 0.86; 95% CI, 0.76-0.98; p<0.025, per doubling). The addition of baseline NT-proBNP (NRI 8.6%, p=0.028; IDI 0.030, p<0.001) and IL-6 (NRI 8.8%, p=0.012; IDI 0.036, p<0.001) improved the clinical risk prediction model and the addition of hsCRP (NRI 6.5%, p=0.069; IDI 0.018, p=0.004) yielded minimal improvement. After incorporating NT-proBNP into the model, the remaining biomarkers added little additional predictive value. CONCLUSIONS: Multiple inflammatory biomarkers independently predicted 90-day death, shock or heart failure; however, they added little value to a clinical prediction model that included NT-proBNP. Future studies of inflammatory biomarkers in STEMI should report incremental value in a prediction model that includes NT-proBNP.
PMID: 23394896
ISSN: 0167-5273
CID: 386892
Percutaneous revascularization and long term clinical outcomes of diabetic patients randomized in the Occluded Artery Trial (OAT)
Overgaard, Christopher B; Dzavik, Vladimir; Buller, Christopher E; Liu, Li; Banasiak, Waldemar; Devlin, Gerard; Maggioni, Aldo P; Leor, Jonathan; Burton, Jeffery R; Reis, Gilmar; Ruzyllo, Witold; Forman, Sandra A; Lamas, Gervasio A; Hochman, Judith S
BACKGROUND: Percutaneous coronary intervention (PCI) of a persistently totally occluded infarct-related artery (IRA) in stable high-risk patients >24h after myocardial infarction (MI) does not reduce the occurrence of death, re-infarction, or heart failure. Diabetic patients are at higher risk for cardiovascular events; we examined their outcomes overall with PCI and optimal medical therapy alone (MED). METHODS: The long-term (7-year) outcomes of 454 diabetic patients (20.6%) randomized to PCI or MED in the Occluded Artery Trial (OAT) were assessed for the composite primary endpoint of death, re-MI, or New York Heart Association class IV heart failure. Diabetics and non-diabetics were compared and outcomes assessed by treatment strategy. RESULTS: The 7-year cumulative primary event rate for diabetic patients was 35.0% vs. 19.4% in the non-diabetic cohort (p<0.001). Multivariable analyses revealed diabetes to be an independent predictor (p<0.01) for the primary outcome, fatal or nonfatal recurrent MI, Class IV Heart Failure (HF), and death. The 7-year cumulative primary event rates were 35.3% in the PCI group vs. 34.5% in the medical therapy group in diabetic patients (p=0.19) and 19.3% in the PCI group vs. 19.5% in the medical therapy group in patients without diabetes (p=0.60). CONCLUSIONS: Despite the higher overall risk conferred by the presence of diabetes, PCI did not improve clinical outcomes in this subpopulation, and is not indicated in otherwise stable patients with a totally occluded infarct-related artery in the sub-acute phase after MI.
PMID: 23582414
ISSN: 0167-5273
CID: 386852
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions
Levine, Glenn N; Bates, Eric R; Blankenship, James C; Bailey, Steven R; Bittl, John A; Cercek, Bojan; Chambers, Charles E; Ellis, Stephen G; Guyton, Robert A; Hollenberg, Steven M; Khot, Umesh N; Lange, Richard A; Mauri, Laura; Mehran, Roxana; Moussa, Issam D; Mukherjee, Debabrata; Nallamothu, Brahmajee K; Ting, Henry H; Jacobs, Alice K; Anderson, Jeffrey L; Albert, Nancy; Creager, Mark A; Ettinger, Steven M; Guyton, Robert A; Halperin, Jonathan L; Hochman, Judith S; Kushner, Frederick G; Ohman, E Magnus; Stevenson, William; Yancy, Clyde W
PMID: 22065485
ISSN: 1522-1946
CID: 386962
Association between bleeding and mortality among women and men with high-risk acute coronary syndromes: Insights from the Early versus Delayed, Provisional Eptifibatide in Acute Coronary Syndromes (EARLY ACS) trial
Kaul, Padma; Tanguay, Jean-Francois; Newby, L Kristin; Hochman, Judith S; Westerhout, Cynthia M; Califf, Robert M; Tricoci, Pierluigi; Gibson, C Michael; Giugliano, Robert P; Harrington, Robert A; Van de Werf, Frans; Armstrong, Paul W
BACKGROUND: Female sex is an established risk factor for bleeding, which is an important safety end point in patients presenting with non-ST-segment elevation acute coronary syndromes (NSTE ACS). However, it is unknown whether the association between bleeding and mortality is modulated by sex in this patient population. METHODS: We examined the interaction between sex and bleeding and 30-day mortality outcomes among 2,975 women and 6,431 men with high-risk NSTE ACS enrolled in the EARLY ACS trial. The Global Utilization of Strategies to Open Occluded Arteries (GUSTO) criteria were used to identify moderate or severe bleeds. RESULTS: Women were older and had more comorbid disease compared with men. Bleeding rates were higher among women (8.2%) than among men (5.5%; P < .01). However, the association of bleeding and 30-day mortality was stronger among men (odds ratio 5.8, 95% CI 3.9-8.8) than among women (odds ratio 1.5, 95% CI 0.8-2.9; sex * bleeding interaction P < .01). Sex differences in the association of bleeding and mortality persisted in a landmark analysis of 120-hour survivors. CONCLUSIONS: In a contemporary high-risk NSTE ACS cohort, women had higher bleeding rates than did men. Paradoxically, the association between bleeding and mortality was worse among men than among women.
PMID: 24093853
ISSN: 0002-8703
CID: 602082