QT Interval Length in Elderly Prostatic Cancer Patients on Anti-Testosterone Treatment.

UNLABELLED: Background: QT segment prolongation is a high risk factor for fatal arrhythmias. Several studies have indicated a possible relation between low testosterone levels and QT interval prolongation. OBJECTIVES: To compare the QT interval length in elderly patients with prostate carcinoma who were on anti-testosterone treatment and those who were not. METHODS: We screened the electrocardiograms (ECGs) of 100 prostate cancer patients divided into two groups: 50 patients on anti-testosterone drug treatment and 50 patients not. QT interval length was measured according to the accepted methods. RESULTS: The mean QTc 12 leads in the entire group was 0.45 ± 0.04 sec, which is close to the upper limit. Mean QTc was actually longer in the control group and there was no QTc difference between the groups after adjustment for possible confounders. Prolonged QTc 12-lead ECG (48% in treated and 54% in non-treated) and lead L2 QT interval (50% in treated and 56% in non-treated) did not differ significantly between the groups. The analysis of QTc 12-lead ECG indicated no significant effects of anti-testosterone drug treatment. Only the use of furosemide was associated with QT prolongation. CONCLUSIONS: The results of this preliminary study do not support our initial concern of an alarmingly prolonged QT interval in the anti-testosterone treated group. However, further prospectively designed studies are needed. In the meanwhile we call for a close follow-up of the QT interval length in patients receiving anti-testosterone treatment.

Speckle tracking imaging in acute inflammatory pericardial diseases.

BACKGROUND: Left ventricular (LV) function in acute perimyocarditis is variable. We evaluated LV function in patients with acute perimyocarditis with speckle tracking. METHODS: Thirty-eight patients with acute perimyocarditis and 20 normal subjects underwent echocardiographic examination. Three-layers strain and twist angle were assessed with a speckle tracking. Follow-up echo was available in 21 patients. RESULTS: Strain was higher in normal subjects than in patients with perimyocarditis. Twist angle was reduced in perimyocarditis--10.9° ± 5.4 versus 17.6° ± 5.8, P < 0.001. Longitudinal strain and twist angle were higher in normal subjects than in patients with perimyocarditis and apparently normal LV function. Follow-up echo in 21 patients revealed improvement in longitudinal strain. CONCLUSIONS: Patients with acute perimyocarditis have lower twist angle, longitudinal and circumferential strain. Patients with perimyocarditis and normal function have lower longitudinal strain and twist angle. Short-term follow-up demonstrated improvement in clinical parameters and longitudinal strain despite of residual regional LV dysfunction.

Intracoronary administration of autologous bone marrow mononuclear cells in patients with chronic ischemic symptomatic cardiomyopathy: 5 years follow-up.

BACKGROUND: Several studies have demonstrated the shortterm safety, feasibility and efficacy of cell transplantation in patients with advanced heart failure. Data on the long-term outcome are lacking. OBJECTIVES: To evaluate the long-term outcome of intracoronary autologous bone marrow administration in patients with stable severe ischemic cardiomyopathy who were not suitable for revascularization. METHODS: We enrolled eight consecutive patients with ischemic cardiomyopathy: all were in NYHA functional class III-IV despite optimal medical treatment. Dobutamine stress echo showed that all had left ventricular ejection fraction < 35% with significant viability or ischemia, or both, in at least two myocardial segments. Based on coronary anatomy none of the patients was suitable for revascularization. Bone marrow was obtained and the cells were injected into all patent conduits after a brief balloon occlusion at a normal coronary segment. Clinical followup was performed periodically at the heart failure clinic, and included electrocardiography, laboratory tests and echocardiography. RESULTS: During 5 years follow-up there were two deaths: one due to leukocytoclastic vasculitis 21 months after intracoronary bone marrow infusion, and the second patient died suddenly during sleep 30 months after the transplant. The other six patients are alive, two of them without any cardiovascular or clinical events. No significant change in systolic and diastolic function was observed on echocardiography. CONCLUSIONS: Despite the small and selected patient group, our long-term follow-up showed a promising outcome for this population of patients suffering from severe cardiac disease. Longer follow-up of a much larger group is needed.

Short and long-term outcome of pregnant women with preexisting dilated cardiomypathy: an NTproBNP and echocardiography-guided study.

BACKGROUND: Little is known of the outcome of pregnant patients with previously diagnosed dilated cardiomyopathy. These patients are usually firmly advised against continuation of the pregnancy. OBJECTIVES: To examine the usefulness of serial echocardiographic follow-up and plasma N-terminal pro-B type natriuretic peptide levels in the management of pregnant women with preexisting DCM. METHODS: We prospectively enrolled pregnant women with DCM either known or diagnosed in the first trimester. Clinical examination and serial echocardiography studies were performed at baseline, at 30 weeks gestation, peripartum, and 3 and 18 months postpartum. Blinded NTproBNP levels were obtained at 30 weeks, at delivery and 3 months postpartum. RESULTS: Between June 2005 and October 2006 we enrolled seven women who fulfilled the study criteria. Delivery and postpartum were complicated in 3 patients (42%): 2 with acute heart failure, which resolved conservatively, and 1 with major pulmonary embolism. The left ventricular ejection fraction was stable throughout the pregnancy (35% +/- 2.8 at baseline, 33% +/- 2.9 at 30 weeks) and postpartum (35% +/- 2.8 at 1 day, 34% +/- 3.1 at 90 days). Similar stable behavior was observed regarding left ventricular dimensions: LV end-systolic diameters 43.3 +/- 2.7 mm and LV end-diastolic diameters 57.3 +/- 3.3 mm at baseline compared with 44.1 +/- 3.1 mm and 58.7 +/- 3.1 mm postpartum, respectively. The NTproBNP levels rose significantly peripartum in all three patients with complications. CONCLUSIONS: Serial NTproBNP levels, as compared to echocardiography, may be a better clinical tool in monitoring and management of pregnant women with preexisting DCM. An early rise in NTproBNP level appears to predict the occurrence of adverse events.

A randomized, placebo-controlled trial to evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamics of a potent inhibitor of poly(ADP-ribose) polymerase (INO-1001) in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of the TIMI 37 trial.

BACKGROUND: Reperfusion injury is a significant complication of the management of ST-elevation MI (STEMI). INO-1001 is a potent inhibitor of poly(ADP-ribose) polymerase (PARP), a mediator of oxidant-induced myocyte dysfunction during reperfusion. METHODS & RESULTS: We assessed the safety and pharmacokinetics of INO-1001 in a randomized, placebo-controlled, single-blind, dose-escalating trial in 40 patients with STEMI undergoing primary percutaneous coronary intervention within 24 h of onset. INO-1001 was well-tolerated. A trend toward more frequent transaminitis was observed with 800 mg. Plasma from INO1001-treated patients reduced in vitro PARP activity >90% at all doses. Serial C-reactive protein and IL-6 levels showed a trend toward blunting of inflammation with INO-1001. The apparent median terminal half-life (t(1/2)) of INO-1001 was 7.5 (25th, 75th: 5.9, 10.2) h. CONCLUSIONS: The results from this first trial of INO-1001 in STEMI support future investigation of INO-1001 as a novel treatment for reperfusion injury.

Long-term (>3 Years) outcome and predictors of clinical events after insertion of sirolimus-eluting stent in one or more native coronary arteries (from the Israeli arm of the e-Cypher registry).

The aim of this study was to evaluate long-term (3.4 years) outcomes and predictors of clinical events in patients treated with sirolimus-eluting stents in the Israeli arm of the e-Cypher registry. From July 2002 to October 2003, 488 patients from 8 medical centers in Israel were enrolled in the e-Cypher registry. Nineteen patients with interventions in venous grafts were excluded from the final analysis. Long-term follow-up was completed for 98% of the remaining patients. There were 29 cases (6.3%) of death (3.9% cardiac and 2.4% noncardiac deaths). According to the broad academic research consortium definition of stent thrombosis, there were 19 cases (4%) of stent thrombosis (incidence density 0.9 cases/100 patient-years). There were 46 cases (9.9%) of target lesion revascularization and 76 cases (16.3%) of major adverse cardiac events (combination of death, myocardial infarction, and target lesion revascularization). Independent predictors of stent thrombosis were renal failure (hazard ratio 9.6, 95% confidence interval 1.9 to 47), stent length (hazard ratio 1.1, 95% confidence interval 1 to 1.2), and the off-label use of sirolimus-eluting stents (hazard ratio 5.3, 95% confidence interval 1.2 to 24). In conclusion, during >3 years of follow-up, stent thrombosis, major adverse cardiac events, and target lesion revascularization continued at constant rates over time. Clinical parameters such as renal failure and procedural parameters such as off-label use and stent length were independent predictors of stent thrombosis.

Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension--a multi-center randomized study.

OBJECTIVE: To evaluate the effects of bosentan on echo-derived hemodynamic measurements, and clinical variables in symptomatic heart failure (HF) patients. METHOD: Multi- center, double-blind, randomized (2:1), placebo-controlled study comparing bosentan (8-125 mg b.i.d.) to placebo in patients with New York Heart Association class IIIb-IV HF, left ventricular ejection fraction <35% and systolic pulmonary artery pressure (SPAP) >40 mm Hg. Primary and secondary endpoints were change from baseline to 20 weeks in SPAP and cardiac index, respectively. Safety endpoints were treatment emergent adverse events (AEs), change in body weight, hemoglobin, hematocrit, systolic blood pressure and diuretic use. RESULTS: Ninety-four patients enrolled: 60 to bosentan, 34 to placebo. There was no significant difference between the 2 arms in SPAP change (0.1 +/- 11.5 mm Hg , 95% confidence limit (CL) -5.4 to 5.2, p = 0.97), cardiac index shift (0.12 +/- 0.45, 95% CL -0.09 to 0.33 , p = 0.24 ) or any of the other 22 echocardiographic measurements obtained. Therapy-duration was longer in the placebo arm, while more patients in the bosentan arm experienced adverse and serious AEs. CONCLUSION: In HF patients with left ventricular dysfunction and secondary pulmonary hypertension, bosentan did not provide any measurable hemodynamic benefit, and was associated with more frequent AEs, requiring drug discontinuation.

Acute myocardial infarction with spontaneous reperfusion: clinical characteristics and optimal timing for revascularization.

BACKGROUND: Spontaneous coronary reperfusion occurs in 7-27% of patients with ST elevation myocardial infarction, and is an independent predictor of myocardial salvage, percutaneous coronary intervention success, and improved outcome. OBJECTIVES: To determine the optimal PCI time for patients admitted to the hospital due to STEMI with SCR. METHODS: We performed a retrospective analysis of all patients admitted to the coronary care unit between July 2002 and November 2004 with a diagnosis of STEMI with SCR. RESULTS: The study group comprised 86 patients. There was not a single reinfarction episode during an observation period of 6579 patient hours. Cardiac catheterization was executed early (< 24 hours from pain onset) in 26 patients and late (> 24 hours) in 55. Pre-PCI angiographic TIMI flow 2-3 was seen in > 95% in both groups. PCI was performed more frequently in the "early" group (P = 0.024), while multi-vessel coronary artery disease (P = 0.094) requiring coronary bypass surgery (P = 0.056) was observed more frequently in the "late catheterization" group. Myocardial infarction and angina pectoris at 30 days occurred more frequently in the early catheterization group (P = 0.039), however no difference in any major adverse cardiac events was detected during long-term follow-up (491 +/- 245 days). CONCLUSIONS: Reinfarction after STEMI with SCR is a rare event. Early PCI in patients with STEMI and SCR, even when executed with aggressive antiplatelet therapy, seems to result in an excess of early MACE without any long-term advantage. Prospective randomized trials should determine the optimal PCI timing for these patients.

Real-time quantitative automatic assessment of left ventricular ejection fraction and regional wall motion by speckle imaging.

BACKGROUND: Echocardiographic assessment of left ventricular function includes calculation of ejection fraction and regional wall motion analysis. Recently, speckle imaging was introduced for quantification of left ventricular function. OBJECTIVES: To assess LVEF by speckle imaging and compare it with Simpson's method, and to assess the regional LV strain obtained by speckle imaging in relation to conventional echocardiographic scores. METHODS: Thirty consecutive patients, 28 with regional LV dysfunction, underwent standard echocardiographic evaluation. LV end-diastolic volume, LV end-systolic volume and EF were calculated independently by speckle imaging and Simpson's rule. The regional peak systolic strain presented by speckle imaging as a bull's-eye map was compared with the conventional visual estimate of echo score. RESULTS: Average EDV obtained by speckle imaging and by Simpson's method was 85.1 vs. 92.7 ml (P = 0.38), average ESV was 49.4 vs. 48.8 ml (P = 0.94), calculated EF was 43.9 vs. 50.5% (P = 0.08). The correlation rate with Simpson's rule was high: 0.92 for EDV, 0.96 for ESV, and 0.89 for EF. The peak systolic strain in two patients without wall motion abnormality was 17.3 +/- 4.7; in normal segments of patients with regional dysfunction, peak systolic strain (13.4 +/- 4.9) was significantly higher than in hypokinetic segments (10.5 +/- 4.5) (P < 0.000001). The strain in hypokinetic segments was significantly higher than in akinetic segments (6.2 +/- 3.6) (P < 0.000001). CONCLUSIONS: Speckle imaging can be successfully used for the assessment of LV volumes and EF. Bull's-eye strain map, created by speckle imaging, can achieve an accurate real-time segmental wall motion analysis.

[ST myocardial infarction with spontaneous coronary reperfusion].

ST elevation myocardial infarction continues to be a major medical problem even in the beginning of the 21st century. Treatment guidelines for these patients are based on multiple randomized clinical trials. In order to minimize myocardial damage, early patency of the infarct relating artery must be accomplished. This is the major difference in the treatment strategy between ST elevation myocardial infarction and other acute coronary syndromes. Primary percutaneous coronary intervention and fibrinolysis are the two treatment modalities for achieving myocardial reperfusion. The subgroup of ST elevation myocardial infarction with spontaneous coronary artery reperfusion carries a more favorable prognosis. This review addresses the clinical characteristics, natural history, prognosis and treatment strategies for this group, with special emphasis on the optimal timing for revascularization, and the role of glycoprotein IIb/IIIa inhibitors.

Intracoronary administration of autologous bone marrow mononuclear cells after induction of short ischemia is safe and may improve hibernation and ischemia in patients with ischemic cardiomyopathy.

BACKGROUND: Recent studies suggest that myocardial administration of stem cells improves perfusion and function of ischemic myocardium. The present study evaluated the safety and efficacy of simple intracoronary administration of mononuclear autologous bone marrow (BM) cells in patients with ischemic cardiomyopathy without revascularization option. METHODS AND RESULTS: We enrolled 6 consecutive patients with ischemic cardiomyopathy, who were in New York Heart Association classes III to IV despite optimal medical treatment without revascularization options and who, on dobutamine stress echocardiograph (DSE), were found to have left ventricular ejection fraction < 35% with significant hibernation and ischemia in at least 2 myocardial segments. BM cell suspension was collected, and on the next day, during coronary angiography, mild ischemia was induced by a short balloon inflation in each coronary conduit with a TIMI flow of > or = 2 followed by slow infusion of up to 50 mL of BM cells suspension to each conduit. At baseline and 4 months' follow-up, patients underwent clinical evaluation, Holter monitoring, and DSE. BM infusion was successful in all patients. One patient developed postprocedure hypotension and troponin increase. At 4 months' follow-up New York Heart Association class improved from 3.5 +/- 0.5 to 2.3 +/- 1.0, P = .04, and resting ejection fraction improved from 25% +/- 7% to 28% +/- 8%, P = .055. We observed improvement in resting wall motion score only in the segments with hibernation in baseline DSE (2.3 +/- 0.5 to 2.0 +/- 0.6, P = .03) and improvement in high-dose dobutamine wall motion score, only in segments showing significant ischemia at baseline DSE (2.5 +/- 0.5 to 2.0 +/- 0.6, P = .001). There were no clinical arrhythmias or increased arrhythmia burden by Holter monitoring. CONCLUSIONS: In patients with severe symptomatic ischemic cardiomyopathy, mild induction of ischemia followed by intracoronary infusion of unmanipulated autologous BM is feasible and safe and may improve hibernation and ischemia.

Anglographic functional characterization of the coronary sinus.

BACKGROUND: Coronary sinus is a venous conduit with dynamic and unclear function with regard to coronary circulation. OBJECTIVES: To describe the dynamic changes of the coronary sinus during the cardiac cycle. METHODS: The angiographic feature of the coronary sinus was evaluated in 30 patients undergoing diagnostic and therapeutic coronary angiography. RESULTS: Prolonged angiographic imaging following coronary injections permitted accurate demonstration of the coronary sinus in all 30 patients. We report, for the first time, that the coronary sinus can be divided into two angiographic functional/anatomic portions, upper and lower. The lower part is prone to a highly dynamic contraction/relaxation pattern, observed in 12 of the 30 patients, while 10 patients had normal and 8 had low contractile pattern on angiography. Clinical assessment of these patients did not identify an association with this motion pattern. CONCLUSIONS: The coronary sinus is an important anatomic/functional structure that should be further investigated in patients with various forms of heart disease.

Atropine-facilitated electrical cardioversion of persistent atrial fibrillation.

Conventional electrical cardioversion failed to restore normal sinus rhythm (NSR) in 49 of 364 patients (13.5%) with persistent atrial fibrillation. After receiving up to 2 mg of atropine, 40 (81%) of these 49 "electrical-refractory" patients were successfully cardioverted to NSR by subsequent attempts of electrical cardioversion.

Acute heart failure: a novel approach to its pathogenesis and treatment.

Acute heart failure (HF) is one of the most common syndromes in emergency medicine, however, its exact pathogenesis has remained largely unknown. Based on clinical and hemodynamic data we have sub-divided acute HF into four syndromes: cardiogenic shock, pulmonary edema, hypertensive crisis and exacerbated HF. Cardiogenic shock is caused by a severe reduction in cardiac power which is not met by an adequate increase in peripheral vascular resistance leading to significant decrease in blood pressure and end organ perfusion. Hence the treatment of cardiogenic shock should be directed at improving cardiac performance (by optimizing filling pressure, intra-aortic balloon pump and immediate revascularization) and administration of peripheral vasoconstrictors. The other acute HF syndromes (pulmonary edema, HTN crisis and exacerbated HF) are caused by a combination of progressive excessive vasoconstriction superimposed on reduced left ventricular functional reserve. The impaired cardiac power and extreme vasoconstriction induce a vicious cycle of afterload mismatch resulting in a dramatic reduction of CO and elevated left ventricular end diastolic pressure, which is transferred backwards to the pulmonary capillaries yielding pulmonary edema. Therefore, the immediate treatment of these acute HF syndromes should be based on the administration of strong, fast-acting intravenous vasodilators such as nitrates or nitroprusside. After initial stabilization, therapy should be directed at reducing recurrent episodes of acute HF, by prevention of repeated episodes of excessive vasoconstriction along with efforts to optimize cardiac function.

The role of cardiac power and systemic vascular resistance in the pathophysiology and diagnosis of patients with acute congestive heart failure.

OBJECTIVE: Conventional hemodynamic indexes (cardiac index (CI), and pulmonary capillary wedge pressure) are of limited value in the diagnosis and treatment of patients with acute congestive heart failure (CHF). PATIENTS AND METHODS: We measured CI, wedge pressure, right atrial pressure (RAP) and mean arterial blood pressure (MAP) in 89 consecutive patients admitted due to acute CHF (exacerbated systolic CHF, n=56; hypertensive crisis, n=5; pulmonary edema, n=11; and cardiogenic shock, n=17) and in two control groups. The two control groups were 11 patients with septic shock and 20 healthy volunteers. Systemic vascular resistance index (SVRi) was calculated as SVRi=(MAP-RAP)/CI. Cardiac contractility was estimated by the cardiac power index (Cpi), calculated as CIxMAP. RESULTS AND DISCUSSION: We found that CI<2.7 l/min/m(2) and wedge pressure >12 mmHg are found consistently in patients with acute CHF. However, these measures often overlapped in patients with different acute CHF syndromes, while Cpi and SVRi permitted more accurate differentiation. Cpi was low in patients with exacerbated systolic CHF and extremely low in patients with cardiogenic shock, while SVRi was increased in patients with exacerbated systolic CHF and extremely high in patients with pulmonary edema. By using a two-dimensional presentation of Cpi vs. SVRi we found that these clinical syndromes can be accurately characterized hemodynamically. The paired measurements of each clinical group segregated into a specific region on the Cpi/SVRi diagnostic graph, that could be mathematically defined by a statistically significant line (Lambda=0.95). Therefore, measurement of SVRi and Cpi and their two-dimensional graphic representation enables accurate hemodynamic diagnosis and follow-up of individual patients with acute CHF.

Improved regional left ventricular function after successful satellite cell grafting in rabbits with myocardial infarction.

OBJECTIVE: To evaluate whether satellite cells injected into infarct areas in rabbits remain viable during 6 weeks follow-up and can improve cardiac function as assessed by echocardiography. METHODS: Myocardial infarction was induced in 16 New Zealand white rabbits, by ligation of the marginalis sinistra artery. Tissue from gluteus muscle biopsies was dissected into small pieces and cultured. Within 2-3 weeks the cells were expanded by 2-3 orders of magnitude and were fluorescent labeled. Single cell pellets for resuspension at >10(6)/1 ml were directly injected into the infarct areas in 8 rabbits. In 8 additional rabbits, 1 ml saline was injected (control). Regional left ventricular function was assessed weekly by 2-D echocardiography until animals were sacrificed. Analysis was performed blind and independently by two experienced echocardiographers, based on the American Society of Echocardiography scheme. RESULTS AND DISCUSSION: Six treated and five control rabbits completed the study. One week after the artery occlusion, left ventricular function scoring did not differ between groups, mean 8.7+/-1.6 vs 8.3+/-1.9 (P=0.74). At 6 weeks post-injection, echocardiographic score was significantly better in the treated group, mean 2.6+/-0.9 vs 6.9+/-2.1 (P=0.002). The treated group showed significant gradual segmental improvement between the first week up to week 6. After sacrifice, macro and microscopic transmural areas showed typical changes of myocardial infarction. Histochemical staining identified viable grafted cells in high density 6 weeks post-transplantation in all grafted hearts. CONCLUSION: Autologous satellite cells (skeletal myofiber), can be successfully grafted into rabbit hearts following myocardial infarction and may induce improved regional left ventricular function.

Improved detection of inferobasal ischemia during dobutamine echocardiography with doppler tissue imaging.

OBJECTIVES: The purpose of this study was quantitative evaluation of the inferobasal segment during dobutamine stress echocardiography using Doppler tissue imaging (DTI). BACKGROUND: Overdiagnosis of myocardial ischemia during dobutamine echocardiography is a common problem. DTI may permit more accurate quantitative diagnosis of ischemia. METHODS: A total of 50 patients with normal contraction of the inferobasal segment at rest were referred for dobutamine stress echocardiography. All underwent coronary angiography. Systolic and diastolic myocardial velocities were measured from apical 2-chamber view at rest and at the peak of dobutamine infusion. RESULTS: Stenosis of the right coronary artery >or= 70% was detected in 11 patients. Conventional stress echocardiography was falsely positive in 10.3% and falsely negative in 27.3%. When DTI was combined with conventional stress echocardiography, sensitivity and specificity was 81.8% and 97.4%, respectively. CONCLUSION: DTI may enhance the diagnosis of inferior ischemia during dobutamine echocardiography and can be added to conventional imaging in the treatment of these patients.