Pub Date : 2002-09-03DOI: 10.1161/01.CIR.0000027585.05868.67
Y. Zhang, C. Hartzell, Michael Narlow, S. Dudley
Background—Cardiomyocytes (CMs) derived from pluripotent embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) have some but not all characteristics of adult myocytes. ESCs have shown the ability to engraft in areas of myocardial damage, which suggests their use in cell transplantation therapy for cardiomyopathy. We studied the arrhythmogenic properties of CMs differentiated from mouse ESCs and ECCs. Methods and Results—CMs derived in vitro were studied in the whole-cell patch-clamp mode. CMs from both sources showed action potential (AP) morphology heterogeneity, with reduced maximum upstroke velocities (dV/dt) and prolonged AP durations. CMs demonstrated prolonged, spontaneous electrical activity in culture. Frequent triggered activity was observed with and without pharmacological enhancement. Phase 2 or 3 early afterdepolarizations could be induced easily by Bay K8644 plus tetraethylammonium chloride (TEA) or [TEA]o after Cs+ replacement for [K+]i, respectively. A combination of bradycardic stimulation, hypokalemia, and quinidine resulted in early afterdepolarizations. Delayed afterdepolarizations could be induced easily and reversibly by hypercalcemia or isoproterenol. Conclusions—ESCs or ECCs differentiated into at least 3 AP phenotypes. CMs showed spontaneous activity, low dV/dt, prolonged AP duration, and easily inducible triggered arrhythmias. These findings raise caution about the use of totipotent ESCs in cell transplantation therapy, because they may act as an unanticipated arrhythmogenic source from any of the 3 classic mechanisms (reentry, automaticity, or triggered activity).
{"title":"Stem Cell-Derived Cardiomyocytes Demonstrate Arrhythmic Potential","authors":"Y. Zhang, C. Hartzell, Michael Narlow, S. Dudley","doi":"10.1161/01.CIR.0000027585.05868.67","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027585.05868.67","url":null,"abstract":"Background—Cardiomyocytes (CMs) derived from pluripotent embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) have some but not all characteristics of adult myocytes. ESCs have shown the ability to engraft in areas of myocardial damage, which suggests their use in cell transplantation therapy for cardiomyopathy. We studied the arrhythmogenic properties of CMs differentiated from mouse ESCs and ECCs. Methods and Results—CMs derived in vitro were studied in the whole-cell patch-clamp mode. CMs from both sources showed action potential (AP) morphology heterogeneity, with reduced maximum upstroke velocities (dV/dt) and prolonged AP durations. CMs demonstrated prolonged, spontaneous electrical activity in culture. Frequent triggered activity was observed with and without pharmacological enhancement. Phase 2 or 3 early afterdepolarizations could be induced easily by Bay K8644 plus tetraethylammonium chloride (TEA) or [TEA]o after Cs+ replacement for [K+]i, respectively. A combination of bradycardic stimulation, hypokalemia, and quinidine resulted in early afterdepolarizations. Delayed afterdepolarizations could be induced easily and reversibly by hypercalcemia or isoproterenol. Conclusions—ESCs or ECCs differentiated into at least 3 AP phenotypes. CMs showed spontaneous activity, low dV/dt, prolonged AP duration, and easily inducible triggered arrhythmias. These findings raise caution about the use of totipotent ESCs in cell transplantation therapy, because they may act as an unanticipated arrhythmogenic source from any of the 3 classic mechanisms (reentry, automaticity, or triggered activity).","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"1 1","pages":"1294-1299"},"PeriodicalIF":0.0,"publicationDate":"2002-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89493318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000027137.96791.6A
S. Rugonfalvi-Kiss, V. Endrész, H. Madsen, K. Burián, J. Duba, Z. Prohászka, I. Karádi, L. Romics, É. Gönczöl, G. Füst, P. Garred
Background—The possible association between coronary artery disease (CAD) and Chlamydia pneumoniae (C pneumoniae) infection is controversial. On the basis of the recent suggestion that mannose-binding lectin (MBL) variant alleles are related to an increased risk of severe atherosclerosis, and on the in vitro interaction of MBL with C pneumoniae, we asked whether MBL might contribute to CAD in conjunction with C pneumoniae. Methods and Results—Antibodies to C pneumoniae were measured by immunofluorescence and MBL alleles were determined by polymerase chain reaction technique in samples from 210 patients with CAD and 257 healthy subjects from Hungary collected between 1995 and 1996. A higher percentage of patients with CAD were anti-C pneumoniae positive as compared with the control group (P =0.058). However, at logistic regression analysis adjusted to age, sex, and serum lipid levels, this difference was confined only to subjects carrying MBL variant alleles (P =0.035, odds ratio 2.63, [95% CI: 1.07 to 6.45]). In contrast, no significant difference was seen in those homozygous for the normal MBL allele (P =0.412). During a 65±5.8-month follow-up period, major outcomes (new myocardial infarction, and/or bypass operation or cardiovascular death) occurred in 11 C pneumoniae positive and 3 C pneumoniae negative patients. In the C pneumoniae positive group, the odds ratio of development of outcomes was 3.27 (95% CI: 1.10 to 9.71, P =0.033) in the carriers of the MBL variant alleles compared with the homozygous carriers of the normal MBL allele. Conclusions—These results indicate that infection with C pneumoniae leads mainly to the development and progression of severe CAD in patients with variation in the MBL gene.
{"title":"Association of Chlamydia pneumoniae With Coronary Artery Disease and Its Progression Is Dependent on the Modifying Effect of Mannose-Binding Lectin","authors":"S. Rugonfalvi-Kiss, V. Endrész, H. Madsen, K. Burián, J. Duba, Z. Prohászka, I. Karádi, L. Romics, É. Gönczöl, G. Füst, P. Garred","doi":"10.1161/01.CIR.0000027137.96791.6A","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027137.96791.6A","url":null,"abstract":"Background—The possible association between coronary artery disease (CAD) and Chlamydia pneumoniae (C pneumoniae) infection is controversial. On the basis of the recent suggestion that mannose-binding lectin (MBL) variant alleles are related to an increased risk of severe atherosclerosis, and on the in vitro interaction of MBL with C pneumoniae, we asked whether MBL might contribute to CAD in conjunction with C pneumoniae. Methods and Results—Antibodies to C pneumoniae were measured by immunofluorescence and MBL alleles were determined by polymerase chain reaction technique in samples from 210 patients with CAD and 257 healthy subjects from Hungary collected between 1995 and 1996. A higher percentage of patients with CAD were anti-C pneumoniae positive as compared with the control group (P =0.058). However, at logistic regression analysis adjusted to age, sex, and serum lipid levels, this difference was confined only to subjects carrying MBL variant alleles (P =0.035, odds ratio 2.63, [95% CI: 1.07 to 6.45]). In contrast, no significant difference was seen in those homozygous for the normal MBL allele (P =0.412). During a 65±5.8-month follow-up period, major outcomes (new myocardial infarction, and/or bypass operation or cardiovascular death) occurred in 11 C pneumoniae positive and 3 C pneumoniae negative patients. In the C pneumoniae positive group, the odds ratio of development of outcomes was 3.27 (95% CI: 1.10 to 9.71, P =0.033) in the carriers of the MBL variant alleles compared with the homozygous carriers of the normal MBL allele. Conclusions—These results indicate that infection with C pneumoniae leads mainly to the development and progression of severe CAD in patients with variation in the MBL gene.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"14 1","pages":"1071-1076"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84557303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000027105.02327.48
A. Chade, M. Rodriguez-Porcel, J. Grande, J. Krier, A. Lerman, J. C. Romero, C. Napoli, L. Lerman
Background—Atherosclerotic renovascular disease may augment deterioration of renal function and ischemic nephropathy compared with other causes of renal artery stenosis (RAS), but the underlying mechanisms remain unclear. This study was designed to test the hypothesis that concurrent early atherosclerosis and hypoperfusion might have greater early deleterious effects on the function and structure of the stenotic kidney. Methods and Results—Regional renal hemodynamics and function at baseline and during vasoactive challenge (acetylcholine or sodium nitroprusside) were quantified in vivo in pigs by electron-beam computed tomography after a 12-week normal (n=7) or hypercholesterolemic (HC, n=7) diet, RAS (n=6), or concurrent HC and a similar degree of RAS (HC+RAS, n=7). Flash-frozen renal tissue was studied ex vivo. Basal cortical perfusion and single-kidney glomerular filtration rate (GFR) were decreased similarly in the stenotic RAS and HC+RAS kidneys, but tubular fluid reabsorption was markedly impaired only in HC+RAS. Perfusion responses to challenge were similarly blunted in the experimental groups. Stimulated GFR increased in normal, HC, and RAS (38.3±3.6%, 36.4±7.6%, and 60.4±9.3%, respectively, P <0.05), but not in HC+RAS (6.5±15.1%). These functional abnormalities in HC+RAS were accompanied by augmented perivascular, tubulointerstitial, and glomerular fibrosclerosis, inflammation, systemic and tissue oxidative stress, and tubular expression of nuclear factor-&kgr;B and inducible nitric oxide synthase. Conclusions—Early chronic HC+RAS imposes distinct detrimental effects on renal function and structure in vivo and in vitro, evident primarily in the tubular and glomerular compartments. Increased oxidative stress may be involved in the proinflammatory and progrowth changes observed in the stenotic HC+RAS kidney, which might potentially facilitate the clinically observed progression to end-stage renal disease.
{"title":"Distinct Renal Injury in Early Atherosclerosis and Renovascular Disease","authors":"A. Chade, M. Rodriguez-Porcel, J. Grande, J. Krier, A. Lerman, J. C. Romero, C. Napoli, L. Lerman","doi":"10.1161/01.CIR.0000027105.02327.48","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027105.02327.48","url":null,"abstract":"Background—Atherosclerotic renovascular disease may augment deterioration of renal function and ischemic nephropathy compared with other causes of renal artery stenosis (RAS), but the underlying mechanisms remain unclear. This study was designed to test the hypothesis that concurrent early atherosclerosis and hypoperfusion might have greater early deleterious effects on the function and structure of the stenotic kidney. Methods and Results—Regional renal hemodynamics and function at baseline and during vasoactive challenge (acetylcholine or sodium nitroprusside) were quantified in vivo in pigs by electron-beam computed tomography after a 12-week normal (n=7) or hypercholesterolemic (HC, n=7) diet, RAS (n=6), or concurrent HC and a similar degree of RAS (HC+RAS, n=7). Flash-frozen renal tissue was studied ex vivo. Basal cortical perfusion and single-kidney glomerular filtration rate (GFR) were decreased similarly in the stenotic RAS and HC+RAS kidneys, but tubular fluid reabsorption was markedly impaired only in HC+RAS. Perfusion responses to challenge were similarly blunted in the experimental groups. Stimulated GFR increased in normal, HC, and RAS (38.3±3.6%, 36.4±7.6%, and 60.4±9.3%, respectively, P <0.05), but not in HC+RAS (6.5±15.1%). These functional abnormalities in HC+RAS were accompanied by augmented perivascular, tubulointerstitial, and glomerular fibrosclerosis, inflammation, systemic and tissue oxidative stress, and tubular expression of nuclear factor-&kgr;B and inducible nitric oxide synthase. Conclusions—Early chronic HC+RAS imposes distinct detrimental effects on renal function and structure in vivo and in vitro, evident primarily in the tubular and glomerular compartments. Increased oxidative stress may be involved in the proinflammatory and progrowth changes observed in the stenotic HC+RAS kidney, which might potentially facilitate the clinically observed progression to end-stage renal disease.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"43 1","pages":"1165-1171"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85220325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000028148.62305.69
A. Capucci, D. Aschieri, M. Piepoli, G. Bardy, E. Iconomu, Maurizio Arvedi
Background—Early defibrillation is the most important intervention affecting survival from sudden cardiac arrest (SCA). To improve public access to early defibrillation, we established Piacenza Progetto Vita (PPV), the first system of out-of-hospital early defibrillation by first-responder volunteers. Methods and Results—The system serves a population of 173 114 residents in the Piacenza region of Italy. Equipment for the system comprises 39 semiautomatic external biphasic defibrillators (AEDs): 12 placed in high-risk locations, 12 in lay-staffed ambulances, and 15 in police cars; 1285 lay volunteers trained in use of the AED, without traditional education in cardiac pulmonary resuscitation, responded to all cases of suspected SCA, in coordination with the Emergency Medical System (EMS). During the first 22 months, 354 SCA occurred (72±12 years, 73% witnessed). The PPV volunteers treated 143 SCA cases (40.4%), with an EMS call-to-arrival time of 4.8±1.2 minutes (versus 6.2±2.3 minutes for EMS, P =0.05). Overall survival rate to hospital discharge was tripled from 3.3% (7 of 211) for EMS intervention to 10.5% (15 of 143) for PPV intervention (P =0.006). The survival rate for witnessed SCA was tripled by PPV: 15.5% versus 4.3% in the EMS-treated group (P =0.002). A “shockable” rhythm was present in 23.8% (34 of 143) of the PPV patients versus 15.6% (33 of 211) of the EMS patients (P =0.055). The survival rate from shockable dysrhythmias was higher for PPV versus EMS: 44.1% (15 of 34) versus 21.2% (7 of 33), P =0.046. The neurologically intact survival rate was higher in PPV-treated versus EMS-treated patients: 8.4% (12 of 143) versus 2.4% (5 of 211), P =0.009. Conclusions—Broad dissemination of AEDs for use by nonmedical volunteers enabled early defibrillation and tripled the survival rate for out-of-hospital SCA.
背景:早期除颤是影响心脏骤停(SCA)患者生存的最重要的干预措施。为了提高公众获得早期除颤的机会，我们建立了Piacenza Progetto Vita (PPV)，这是第一个由急救志愿者提供的院外早期除颤系统。方法与结果:该系统为意大利皮亚琴察地区173114名居民提供服务。该系统的设备包括39台半自动体外双相除颤器(aed): 12台安装在高风险地点，12台安装在非专业人员的救护车上，15台安装在警车上;1285名接受过AED使用培训的非专业志愿者，没有接受过传统的心肺复苏教育，在紧急医疗系统(EMS)的配合下，对所有疑似SCA病例做出了反应。前22个月发生354例SCA(72±12年，73%)。PPV志愿者治疗143例SCA (40.4%)， EMS呼叫到达时间为4.8±1.2分钟(EMS为6.2±2.3分钟，P =0.05)。总生存率从EMS干预组的3.3%(211人中7人)到PPV干预组的10.5%(143人中15人)增加了两倍(P =0.006)。经PPV治疗的SCA患者的生存率为15.5%，而ems治疗组为4.3% (P =0.002)。PPV患者中有23.8%(143例中的34例)存在“震荡性”心律，而EMS患者中有15.6%(211例中的33例)存在“震荡性”心律(P =0.055)。与EMS相比，PPV的休克性心律失常生存率更高:44.1% (15 / 34)vs 21.2% (7 / 33)， P =0.046。ppv治疗的神经系统完整生存率高于ems治疗的患者:8.4%(143 / 12)对2.4% (211 / 5)，P =0.009。结论:在非医疗志愿者中广泛推广使用aed能够实现早期除颤，并使院外SCA的生存率提高了两倍。
{"title":"Tripling Survival From Sudden Cardiac Arrest Via Early Defibrillation Without Traditional Education in Cardiopulmonary Resuscitation","authors":"A. Capucci, D. Aschieri, M. Piepoli, G. Bardy, E. Iconomu, Maurizio Arvedi","doi":"10.1161/01.CIR.0000028148.62305.69","DOIUrl":"https://doi.org/10.1161/01.CIR.0000028148.62305.69","url":null,"abstract":"Background—Early defibrillation is the most important intervention affecting survival from sudden cardiac arrest (SCA). To improve public access to early defibrillation, we established Piacenza Progetto Vita (PPV), the first system of out-of-hospital early defibrillation by first-responder volunteers. Methods and Results—The system serves a population of 173 114 residents in the Piacenza region of Italy. Equipment for the system comprises 39 semiautomatic external biphasic defibrillators (AEDs): 12 placed in high-risk locations, 12 in lay-staffed ambulances, and 15 in police cars; 1285 lay volunteers trained in use of the AED, without traditional education in cardiac pulmonary resuscitation, responded to all cases of suspected SCA, in coordination with the Emergency Medical System (EMS). During the first 22 months, 354 SCA occurred (72±12 years, 73% witnessed). The PPV volunteers treated 143 SCA cases (40.4%), with an EMS call-to-arrival time of 4.8±1.2 minutes (versus 6.2±2.3 minutes for EMS, P =0.05). Overall survival rate to hospital discharge was tripled from 3.3% (7 of 211) for EMS intervention to 10.5% (15 of 143) for PPV intervention (P =0.006). The survival rate for witnessed SCA was tripled by PPV: 15.5% versus 4.3% in the EMS-treated group (P =0.002). A “shockable” rhythm was present in 23.8% (34 of 143) of the PPV patients versus 15.6% (33 of 211) of the EMS patients (P =0.055). The survival rate from shockable dysrhythmias was higher for PPV versus EMS: 44.1% (15 of 34) versus 21.2% (7 of 33), P =0.046. The neurologically intact survival rate was higher in PPV-treated versus EMS-treated patients: 8.4% (12 of 143) versus 2.4% (5 of 211), P =0.009. Conclusions—Broad dissemination of AEDs for use by nonmedical volunteers enabled early defibrillation and tripled the survival rate for out-of-hospital SCA.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"437 1","pages":"1065-1070"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77009439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000030935.89559.04
U. Jorde, T. Vittorio, S. Katz, P. Colombo, F. Latif, T. L. Le Jemtel
Background—Plasma aldosterone levels are elevated in patients with chronic heart failure (CHF) taking angiotensin-converting enzyme (ACE) inhibitors. Elevated aldosterone levels may reflect incomplete inhibition of the vascular converting enzyme during long-term ACE inhibition. We simultaneously measured plasma aldosterone levels and the degree of inhibition of the vascular converting enzyme in patients with CHF. Methods and Results—Thirty-four subjects with CHF receiving the maximum recommended doses of ACE inhibitors for a duration of 3 to 105 months were studied. The pressor response to exogenous angiotensin I (AI) was measured and normalized for the pressor response to angiotensin II (AII) to assess inhibition of the vascular converting enzyme (AII/AI ratio). Aldosterone levels were determined by solid-phase radioimmunoassay. Eleven of the 34 subjects had plasma aldosterone levels above the upper limit of normal, ie, >15.0 ng/dL. Seven of these 11 subjects (64%) had an AII/AI ratio ≤0.05, indicating complete inhibition of the vascular converting enzyme. In the entire cohort, the AII/AI ratio did not correlate with the duration of ACE inhibitor therapy. Conclusions—Plasma aldosterone levels are elevated in patients with CHF during long-term ACE inhibitor therapy despite complete inhibition of the vascular converting enzyme. Complete inhibition of the vascular converting enzyme does not obviate the need for aldosterone receptor blockade in patients with CHF.
{"title":"Elevated Plasma Aldosterone Levels Despite Complete Inhibition of the Vascular Angiotensin-Converting Enzyme in Chronic Heart Failure","authors":"U. Jorde, T. Vittorio, S. Katz, P. Colombo, F. Latif, T. L. Le Jemtel","doi":"10.1161/01.CIR.0000030935.89559.04","DOIUrl":"https://doi.org/10.1161/01.CIR.0000030935.89559.04","url":null,"abstract":"Background—Plasma aldosterone levels are elevated in patients with chronic heart failure (CHF) taking angiotensin-converting enzyme (ACE) inhibitors. Elevated aldosterone levels may reflect incomplete inhibition of the vascular converting enzyme during long-term ACE inhibition. We simultaneously measured plasma aldosterone levels and the degree of inhibition of the vascular converting enzyme in patients with CHF. Methods and Results—Thirty-four subjects with CHF receiving the maximum recommended doses of ACE inhibitors for a duration of 3 to 105 months were studied. The pressor response to exogenous angiotensin I (AI) was measured and normalized for the pressor response to angiotensin II (AII) to assess inhibition of the vascular converting enzyme (AII/AI ratio). Aldosterone levels were determined by solid-phase radioimmunoassay. Eleven of the 34 subjects had plasma aldosterone levels above the upper limit of normal, ie, >15.0 ng/dL. Seven of these 11 subjects (64%) had an AII/AI ratio ≤0.05, indicating complete inhibition of the vascular converting enzyme. In the entire cohort, the AII/AI ratio did not correlate with the duration of ACE inhibitor therapy. Conclusions—Plasma aldosterone levels are elevated in patients with CHF during long-term ACE inhibitor therapy despite complete inhibition of the vascular converting enzyme. Complete inhibition of the vascular converting enzyme does not obviate the need for aldosterone receptor blockade in patients with CHF.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"181 1","pages":"1055-1057"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80232916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000027566.51212.3F
T. Bowers, W. O’Neill, M. Pica, J. Goldstein
Background—Although proximal right coronary artery (RCA) occlusion is the culprit commonly responsible for acute right ventricular (RV) infarction (RVI), the severity of RV dysfunction ranges broadly. This study was designed to delineate the patterns of coronary compromise that determine the magnitude of RV ischemic dysfunction. Methods and Results—In 125 patients with acute inferior myocardial infarction undergoing emergency angiography, the culprit infarct lesion was identified, RV branch flow assessed (TIMI flows and frame counts), and individual patient RV perfusion indices calculated by separately averaging the branch flows and frame counts, which were correlated with RV wall motion by ultrasound. RVI occurred in 53 (42%) patients, with the RCA as the culprit vessel and the lesion sufficiently proximal to compromise flow in at least one RV branch in all cases, thereby resulting in depressed RV perfusion (flow index, 0.7±0.2). In patients without RVI, the RCA was the culprit in 89%; the circumflex, in 11%. RCA culprits were proximal in 19% of such cases, with lack of RVI explained by preserved RV perfusion (flow index, 2.7±0.3;P =0.001) attributable to at least 1 patent RV branch, spontaneous reperfusion, or prominent collaterals. Overall, there was a strong correlation between RV perfusion and wall motion (Spearman correlation coefficient=0.79). Conclusions—Proximal RCA occlusion compromising RV branch perfusion commonly results in RV ischemic dysfunction. In some cases with proximal RCA culprits, collaterals or spontaneous reperfusion preserve RV performance.
{"title":"Patterns of Coronary Compromise Resulting in Acute Right Ventricular Ischemic Dysfunction","authors":"T. Bowers, W. O’Neill, M. Pica, J. Goldstein","doi":"10.1161/01.CIR.0000027566.51212.3F","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027566.51212.3F","url":null,"abstract":"Background—Although proximal right coronary artery (RCA) occlusion is the culprit commonly responsible for acute right ventricular (RV) infarction (RVI), the severity of RV dysfunction ranges broadly. This study was designed to delineate the patterns of coronary compromise that determine the magnitude of RV ischemic dysfunction. Methods and Results—In 125 patients with acute inferior myocardial infarction undergoing emergency angiography, the culprit infarct lesion was identified, RV branch flow assessed (TIMI flows and frame counts), and individual patient RV perfusion indices calculated by separately averaging the branch flows and frame counts, which were correlated with RV wall motion by ultrasound. RVI occurred in 53 (42%) patients, with the RCA as the culprit vessel and the lesion sufficiently proximal to compromise flow in at least one RV branch in all cases, thereby resulting in depressed RV perfusion (flow index, 0.7±0.2). In patients without RVI, the RCA was the culprit in 89%; the circumflex, in 11%. RCA culprits were proximal in 19% of such cases, with lack of RVI explained by preserved RV perfusion (flow index, 2.7±0.3;P =0.001) attributable to at least 1 patent RV branch, spontaneous reperfusion, or prominent collaterals. Overall, there was a strong correlation between RV perfusion and wall motion (Spearman correlation coefficient=0.79). Conclusions—Proximal RCA occlusion compromising RV branch perfusion commonly results in RV ischemic dysfunction. In some cases with proximal RCA culprits, collaterals or spontaneous reperfusion preserve RV performance.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"38 1","pages":"1104-1109"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81531118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000027568.39540.4B
R. Mehta, R. Manfredini, F. Hassan, U. Sechtem, E. Bossone, J. Oh, Jeanna V. Cooper, Dean E. Smith, F. Portaluppi, M. Penn, S. Hutchison, C. Nienaber, E. Isselbacher, K. Eagle
Background—Chronobiological rhythms have been shown to influence the occurrence of a variety of cardiovascular disorders. However, the effects of the time of the day, the day of the week, or monthly/seasonal changes on acute aortic dissection (AAD) have not been well studied. Methods and Results—Accordingly, we evaluated 957 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2000 (mean age 62±14 years, type A 61%). A &khgr;2 test for goodness of fit and partial Fourier analysis were used to evaluate nonuniformity and rhythmicity of AAD during circadian, weekly, and monthly periods. A significantly higher frequency of AAD occurred from 6:00 am to 12:00 noon compared with other time periods (12:00 noon to 6:00 pm, 6:00 pm to 12:00 midnight, and 12:00 midnight to 6:00 am;P <0.001 by &khgr;2 test). Fourier analysis showed a highly significant circadian variation (P <0.001) with a peak between 8:00 am and 9:00 am. Although no significant variation was found for the day of the week, the frequency of AAD was significantly higher during winter (P =0.008 versus other seasons by &khgr;2 test). Fourier analysis confirmed this monthly variation with a peak in January (P <0.001). Subgroup analysis identified a significant association for all subgroups with circadian rhythmicity. However, seasonal/monthly variations were observed only among patients aged <70 years, those with type B AAD, and those without hypertension or diabetes. Conclusions—Similar to other cardiovascular conditions, AAD exhibits significant circadian and seasonal/monthly variations. Our findings may have important implications for the prevention of AAD by tailoring treatment strategies to ensure maximal benefits during the vulnerable periods.
{"title":"Chronobiological Patterns of Acute Aortic Dissection","authors":"R. Mehta, R. Manfredini, F. Hassan, U. Sechtem, E. Bossone, J. Oh, Jeanna V. Cooper, Dean E. Smith, F. Portaluppi, M. Penn, S. Hutchison, C. Nienaber, E. Isselbacher, K. Eagle","doi":"10.1161/01.CIR.0000027568.39540.4B","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027568.39540.4B","url":null,"abstract":"Background—Chronobiological rhythms have been shown to influence the occurrence of a variety of cardiovascular disorders. However, the effects of the time of the day, the day of the week, or monthly/seasonal changes on acute aortic dissection (AAD) have not been well studied. Methods and Results—Accordingly, we evaluated 957 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2000 (mean age 62±14 years, type A 61%). A &khgr;2 test for goodness of fit and partial Fourier analysis were used to evaluate nonuniformity and rhythmicity of AAD during circadian, weekly, and monthly periods. A significantly higher frequency of AAD occurred from 6:00 am to 12:00 noon compared with other time periods (12:00 noon to 6:00 pm, 6:00 pm to 12:00 midnight, and 12:00 midnight to 6:00 am;P <0.001 by &khgr;2 test). Fourier analysis showed a highly significant circadian variation (P <0.001) with a peak between 8:00 am and 9:00 am. Although no significant variation was found for the day of the week, the frequency of AAD was significantly higher during winter (P =0.008 versus other seasons by &khgr;2 test). Fourier analysis confirmed this monthly variation with a peak in January (P <0.001). Subgroup analysis identified a significant association for all subgroups with circadian rhythmicity. However, seasonal/monthly variations were observed only among patients aged <70 years, those with type B AAD, and those without hypertension or diabetes. Conclusions—Similar to other cardiovascular conditions, AAD exhibits significant circadian and seasonal/monthly variations. Our findings may have important implications for the prevention of AAD by tailoring treatment strategies to ensure maximal benefits during the vulnerable periods.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"18 1","pages":"1110-1115"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91372629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000027818.15792.1E
B. Gerber, J. Garot, D. Bluemke, Katherine C. Wu, J. Lima
Background—Contrast-enhanced (CE) MRI demonstrates a pattern of hypoenhancement early after contrast injection in acute myocardial infarction (MI) and a pattern of hyperenhancement late after contrast injection. Because the significance of these CE patterns for myocardial viability remains debated, we evaluated their diagnostic accuracy to quantitatively predict late functional improvement of regional contractility. Methods and Results—Twenty patients underwent CE and tagged MRI at 4 days and again at 7 months after acute MI. Resting circumferential shortening strain (Ecc) was analyzed in 24 segments per patient, and its improvement was correlated with the presence or absence of the CE patterns. Immediately after MI, 389 segments were considered dysfunctional because of having less than mean±2 SD Ecc of the remote region (−18±4%). At follow-up, significant improvement of Ecc occurred in 170 dysfunctional segments with normal CE (from −4±7% to −12±7%, P <0.001) but not in 60 segments with early hypoenhancement (from −2±6% to −6±9% Ecc, P =NS). In 240 dysfunctional segments with delayed hyperenhancement, the improvement of Ecc (from −2±6% to −5±8%, P <0.001) decreased with increasing transmural extent of hyperenhancement. Receiver operating characteristic analysis demonstrated that absence of delayed hyperenhancement, compared with absence of early hypoenhancement, had better sensitivity (82% versus 19%, respectively;P <0.001) and accuracy (74% versus 49%, respectively;P <0.001) in predicting recovery of Ecc to any given level. Conclusions—Compared with lack of early hypoenhancement, lack of delayed hyperenhancement has better diagnostic accuracy in predicting functional improvement in dysfunctional segments. The early hypoenhanced regions, which represent only the fraction of infarcted tissue with concomitant microvascular obstruction, greatly underestimate the amount of irreversibly injured myocardium present after acute MI.
{"title":"Accuracy of Contrast-Enhanced Magnetic Resonance Imaging in Predicting Improvement of Regional Myocardial Function in Patients After Acute Myocardial Infarction","authors":"B. Gerber, J. Garot, D. Bluemke, Katherine C. Wu, J. Lima","doi":"10.1161/01.CIR.0000027818.15792.1E","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027818.15792.1E","url":null,"abstract":"Background—Contrast-enhanced (CE) MRI demonstrates a pattern of hypoenhancement early after contrast injection in acute myocardial infarction (MI) and a pattern of hyperenhancement late after contrast injection. Because the significance of these CE patterns for myocardial viability remains debated, we evaluated their diagnostic accuracy to quantitatively predict late functional improvement of regional contractility. Methods and Results—Twenty patients underwent CE and tagged MRI at 4 days and again at 7 months after acute MI. Resting circumferential shortening strain (Ecc) was analyzed in 24 segments per patient, and its improvement was correlated with the presence or absence of the CE patterns. Immediately after MI, 389 segments were considered dysfunctional because of having less than mean±2 SD Ecc of the remote region (−18±4%). At follow-up, significant improvement of Ecc occurred in 170 dysfunctional segments with normal CE (from −4±7% to −12±7%, P <0.001) but not in 60 segments with early hypoenhancement (from −2±6% to −6±9% Ecc, P =NS). In 240 dysfunctional segments with delayed hyperenhancement, the improvement of Ecc (from −2±6% to −5±8%, P <0.001) decreased with increasing transmural extent of hyperenhancement. Receiver operating characteristic analysis demonstrated that absence of delayed hyperenhancement, compared with absence of early hypoenhancement, had better sensitivity (82% versus 19%, respectively;P <0.001) and accuracy (74% versus 49%, respectively;P <0.001) in predicting recovery of Ecc to any given level. Conclusions—Compared with lack of early hypoenhancement, lack of delayed hyperenhancement has better diagnostic accuracy in predicting functional improvement in dysfunctional segments. The early hypoenhanced regions, which represent only the fraction of infarcted tissue with concomitant microvascular obstruction, greatly underestimate the amount of irreversibly injured myocardium present after acute MI.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"64 1","pages":"1083-1089"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79516115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000026805.41747.54
G. Theilmeier, P. Verhamme, S. Dymarkowski, H. Beck, H. Bernar, M. Lox, S. Janssens, M. Herregods, E. Verbeken, D. Collen, K. Plate, W. Flameng, P. Holvoet
Background—Hypercholesterolemia induces functional and structural changes of the microvasculature and reduces coronary flow reserve in humans and experimental animals. The effect of hypercholesterolemia on left ventricular (LV) function in the absence of coronary stenosis is, however, unknown. Our objective was therefore to assess the effect of hypercholesterolemia and cholesterol withdrawal on LV function in the presence of advanced coronary plaques that do not cause stenosis. Methods and Results—Twenty-eight minipigs on cholesterol diet for 34 weeks and 16 control pigs were studied. Seven hypercholesterolemic pigs were withdrawn from the diet for 26 weeks. LV function was assessed with cine-MRI, myocardial blood flow with colored microspheres, and capillary density with immunohistochemistry, and microvascular endothelial cell apoptosis with terminal dUTP nick-end labeling staining. Hypercholesterolemia (17±8 versus 268±150 versus 12±10 mg/dL LDL cholesterol, control versus hypercholesterolemic versus cholesterol withdrawal;P <0.001) induced atherosclerosis but not stenosis in the left coronary artery. Baseline cardiac output, ejection fraction, and stroke volume were similar in control and hypercholesterolemic pigs. In dobutamine stress test, cardiac output (P <0.05) and stroke volume (P <0.01) were lower in hypercholesterolemic pigs compared with controls. The impaired response to dobutamine was reversible by dietary cholesterol withdrawal. Hypercholesterolemia reduced endomyocardial coronary flow reserve (P <0.01) and capillary density (P <0.05) and induced capillary endothelial cell apoptosis. Hypercholesterolemic pigs failed to reduce vascular resistance in response to increased LV workload and pharmacological vasodilation. Conclusion—LDL hypercholesterolemia in minipigs impaired LV response to dobutamine stress in the absence of coronary stenosis.
{"title":"Hypercholesterolemia in Minipigs Impairs Left Ventricular Response to Stress: Association With Decreased Coronary Flow Reserve and Reduced Capillary Density","authors":"G. Theilmeier, P. Verhamme, S. Dymarkowski, H. Beck, H. Bernar, M. Lox, S. Janssens, M. Herregods, E. Verbeken, D. Collen, K. Plate, W. Flameng, P. Holvoet","doi":"10.1161/01.CIR.0000026805.41747.54","DOIUrl":"https://doi.org/10.1161/01.CIR.0000026805.41747.54","url":null,"abstract":"Background—Hypercholesterolemia induces functional and structural changes of the microvasculature and reduces coronary flow reserve in humans and experimental animals. The effect of hypercholesterolemia on left ventricular (LV) function in the absence of coronary stenosis is, however, unknown. Our objective was therefore to assess the effect of hypercholesterolemia and cholesterol withdrawal on LV function in the presence of advanced coronary plaques that do not cause stenosis. Methods and Results—Twenty-eight minipigs on cholesterol diet for 34 weeks and 16 control pigs were studied. Seven hypercholesterolemic pigs were withdrawn from the diet for 26 weeks. LV function was assessed with cine-MRI, myocardial blood flow with colored microspheres, and capillary density with immunohistochemistry, and microvascular endothelial cell apoptosis with terminal dUTP nick-end labeling staining. Hypercholesterolemia (17±8 versus 268±150 versus 12±10 mg/dL LDL cholesterol, control versus hypercholesterolemic versus cholesterol withdrawal;P <0.001) induced atherosclerosis but not stenosis in the left coronary artery. Baseline cardiac output, ejection fraction, and stroke volume were similar in control and hypercholesterolemic pigs. In dobutamine stress test, cardiac output (P <0.05) and stroke volume (P <0.01) were lower in hypercholesterolemic pigs compared with controls. The impaired response to dobutamine was reversible by dietary cholesterol withdrawal. Hypercholesterolemia reduced endomyocardial coronary flow reserve (P <0.01) and capillary density (P <0.05) and induced capillary endothelial cell apoptosis. Hypercholesterolemic pigs failed to reduce vascular resistance in response to increased LV workload and pharmacological vasodilation. Conclusion—LDL hypercholesterolemia in minipigs impaired LV response to dobutamine stress in the absence of coronary stenosis.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"1148 1","pages":"1140-1146"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74151279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-27DOI: 10.1161/01.CIR.0000030936.97158.C4
A. Abbate, R. Bussani, G. Biondi-Zoccai, R. Rossiello, F. Silvestri, F. Baldi, L. Biasucci, A. Baldi
Background—Myocardial apoptosis persists beyond the acute phases of acute myocardial infarction (AMI) and is associated with left ventricular (LV) remodeling. Infarct-related artery (IRA) patency is considered a favorable prognostic factor after AMI and may be associated with more favorable LV remodeling because of reduced apoptosis at the site of AMI. The aim of this study was to assess the influence of IRA status on apoptotic rate (AR) in the hearts of subjects dying late after AMI. Methods and Results—We used colocalization for in situ end-labeling of DNA fragmentation and immunohistochemistry for caspase-3 to calculate the AR at time of death (12 to 62 days after AMI) in 16 hearts with persistently occluded IRAs and in 8 hearts with patent IRAs. No significant differences were found when comparing the clinical characteristics of the 2 groups. Occluded IRA was associated with significantly higher AR at site of infarction (25.8% [interquartile range 20.9% to 28.5%] versus 2.3% [interquartile range 0.6% to 5.0%], P <0.001). This strong correlation between IRA occlusion and AR remained statistically significant even after correction for clinical characteristics such as sex, age, history of previous additional AMI or heart failure, transmural AMI, anterior AMI, fibrinolytic treatment, time from AMI to death, trauma as cause of death, and multivessel coronary disease (P =0.003). Conclusions—A significantly higher AR was associated with persistent IRA occlusion late post-AMI. These data may suggest that the post-AMI benefits observed with a patent IRA (the “open-artery hypothesis”) may in part be due to reduced myocardial apoptosis.
{"title":"Persistent Infarct–Related Artery Occlusion Is Associated With an Increased Myocardial Apoptosis at Postmortem Examination in Humans Late After an Acute Myocardial Infarction","authors":"A. Abbate, R. Bussani, G. Biondi-Zoccai, R. Rossiello, F. Silvestri, F. Baldi, L. Biasucci, A. Baldi","doi":"10.1161/01.CIR.0000030936.97158.C4","DOIUrl":"https://doi.org/10.1161/01.CIR.0000030936.97158.C4","url":null,"abstract":"Background—Myocardial apoptosis persists beyond the acute phases of acute myocardial infarction (AMI) and is associated with left ventricular (LV) remodeling. Infarct-related artery (IRA) patency is considered a favorable prognostic factor after AMI and may be associated with more favorable LV remodeling because of reduced apoptosis at the site of AMI. The aim of this study was to assess the influence of IRA status on apoptotic rate (AR) in the hearts of subjects dying late after AMI. Methods and Results—We used colocalization for in situ end-labeling of DNA fragmentation and immunohistochemistry for caspase-3 to calculate the AR at time of death (12 to 62 days after AMI) in 16 hearts with persistently occluded IRAs and in 8 hearts with patent IRAs. No significant differences were found when comparing the clinical characteristics of the 2 groups. Occluded IRA was associated with significantly higher AR at site of infarction (25.8% [interquartile range 20.9% to 28.5%] versus 2.3% [interquartile range 0.6% to 5.0%], P <0.001). This strong correlation between IRA occlusion and AR remained statistically significant even after correction for clinical characteristics such as sex, age, history of previous additional AMI or heart failure, transmural AMI, anterior AMI, fibrinolytic treatment, time from AMI to death, trauma as cause of death, and multivessel coronary disease (P =0.003). Conclusions—A significantly higher AR was associated with persistent IRA occlusion late post-AMI. These data may suggest that the post-AMI benefits observed with a patent IRA (the “open-artery hypothesis”) may in part be due to reduced myocardial apoptosis.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"40 1","pages":"1051-1054"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89505199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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