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The aim of the study was to investigate the effect of beta-blocker treatment on a large cohort of patients with coronary artery disease in functional classes II and III according to the New York Heart Association (NYHA) classification. Among 11,575 patients with coronary artery disease screened for participation, but not included in the Bezafibrate Infarction Prevention (BIP) study, 3,225 (28%) were in NYHA classes II and III. In the latter group of patients we compared the prognosis of 1,109 (34%) treated with beta blockers with 2,116 counterparts not receiving beta-blocker therapy. After a mean follow-up of 4 years, all-cause and cardiac mortality rates were significantly lower among beta-blocker users, 9% and 5%, respectively, than among beta-blocker nonusers, 17% and 11%, respectively (p <0.01 for both). After multivariate adjustment, treatment with beta blockers was associated with a lower all-cause mortality risk (hazards ratio [HR] 0.62, 95% confidence interval [CI] 0.49 to 0.78), and a lower cardiac mortality risk (HR = 0.61, 95% CI 0.45 to 0.83) than was no treatment with a beta blocker. Lower total mortality risk was noted among patients in NYHA class II (HR 0.63, 95% CI 0.48 to 0.82) and in NYHA class III (HR 0.57, 95% CI 0.37 to 0.87) as well as in patients with (HR 0.62, 95% CI 0.48 to 0.81) or without (HR 0.70, 95% CI 0.45 to 1.09) a previous myocardial infarction. We conclude that beta-blocker therapy in coronary patients in NYHA classes II or III is safe and associated with a lower risk for all-cause and cardiac mortality. [ABSTRACT FROM AUTHOR]

We report on measurements of three-body recombination loss rates in an ultracold gas of 7Li atoms in the extremely nonuniversal regime where the two-body scattering length vanishes. We show that the loss rate coefficient is well defined and can be described by two-body parameters only: the scattering length a and the effective range Re. We find the rate to be energy independent, and, by connecting our results with previously reported measurements in the universal limit, we cover the behavior of the three-body recombination rate in the whole range from weak to strong two-body interactions. We identify a nontrivial magnetic field value in the nonuniversal regime where the rate should be suppressed. [ABSTRACT FROM AUTHOR]

Patients sustaining an ST-segment elevation myocardial infarction (STEMI) frequently develop pulmonary congestion or pulmonary edema (PED). We previously showed that lung impedance (LI) threshold decrease of 12% to 14% from baseline during admission for STEMI marks the onset of the transition zone from interstitial to alveolar edema and predicts evolution to PED with 98% probability. The aim of this study was to prove that pre-emptive LI-guided treatment may prevent PED and improve clinical outcomes. Five hundred sixty patients with STEMI and no signs of heart failure underwent LI monitoring for 84 ± 36 hours. Maximal LI decrease throughout monitoring did not exceed 12% in 347 patients who did not develop PED (group 1). In 213 patients LI reached the threshold level and, although still asymptomatic (Killip class I), these patients were then randomized to conventional (group 2, n = 142) or LI-guided (group 3, n = 71) pre-emptive therapy. In group 3, treatment was initiated at randomization (LI = −13.8 ± 0.6%). In contrast, conventionally treated patients (group 2) were treated only at onset of dyspnea occurring 4.1 ± 3.1 hours after randomization (LI = −25.8 ± 4.3%, p <0.001). All patients in group 2 but only 8 patients in group 3 (11%) developed Killip class II to IV PED (p <0.001). Unadjusted hospital mortality, length of stay, 1-year readmission rate, 6-year mortality, and new-onset heart failure occurred less in group 3 (p <0.001). Multivariate analysis adjusted for age, left ventricular ejection fraction, risk factors, peak creatine kinase, and admission creatinine and hemoglobin levels showed improved clinical outcome in group 3 (p <0.001). In conclusion, LI-guided pre-emptive therapy in patients with STEMI decreases the incidence of in-hospital PED and results in better short- and long-term outcomes. [ABSTRACT FROM AUTHOR]

We develop an experimental technique for rf association of Efimov trimers from a three-atom continuum. We apply it to probe the lowest accessible Efimov energy level in bosonic lithium in the region where strong deviations from the universal behavior are expected, and provide a quantitative study of this effect. The position of the Efimov resonance at the atom-dimer threshold, measured using a different experimental technique, concurs with the rf association results. [ABSTRACT FROM AUTHOR]

Background: Monitoring of lung fluid content (LFC) in order to predict acute heart failure (AHF) during acute myocardial infarction (AMI) is an unmet challenge. Aim: To evaluate in AMI patients the ability of proposed radiological score (RS), which is the sum of selected radiological signs of congestion, to reflect correctly LFC, as assessed with repeat physical examinations and lung impedance (LI) measurements. Methods: Chest X-rays were taken at baseline, when rales were detected, whenever indicated, and at conclusion of monitoring. RS grading for LFC assessment was: RS == 0--1 for normal X-ray, RS == 2--4 for interstitial congestion, and RS values of 5--6, 7--8 and 9--10 signified mild, moderate and severe alveolar edema, respectively. Results: 624 AMI patients without AHF at baseline were monitored (94 ±± 42 h). 476 patients (76%) with baseline RS of 0.3 ±± 0.5 did not develop AHF. Overt AHF developed in 148 patients (24%) during monitoring; baseline RS (0.6 ±± 0.8) reached 5.4 ±± 0.7, 7.0 ±± 0.8, and 9.8 ±± 0.5 at the stages of mild, moderate, and severe alveolar edema, respectively. AHF resolved with treatment. RS decreased to 1.5 ±± 1.3 ( P < 0.01) and correlated with physical examination (r == 0.6, P < 0.01) and LI (r == −−0.9, P < 0.01). Conclusion: RS correlated well with findings on physical examination during AHF and closely correlated with LI. [ABSTRACT FROM AUTHOR]

Patients with recurrent acute myocardial infarction (AMI), who represent ≤35% of hospitalized patients with AMI, are at an increased risk of complications and death. Our study purpose was to compare the treatment and outcome of patients hospitalized with recurrent acute ST-segment elevation myocardial infarction (STEMI) from 1998 to 2006 with those of patients with a first STEMI. We performed 5 biennial nationwide 2-month surveys during 1998 to 2006, collecting data prospectively from all patients hospitalized for AMI or acute coronary syndrome in all 25 coronary care units in Israel. The present cohort included 4,543 patients with STEMI, 3,679 (76%) with first and 864 (24%) with recurrent STEMI. The patients with recurrent STEMI were older (66 ± 13 vs 62 ± 13 years), had greater rates of diabetes, hypertension, and previous angina, had a worse Killip class on admission, and experienced more in-hospital complications. The all-cause hospital crude mortality rate was 8.1% in patients with recurrent STEMI versus 5.5% in those with a first STEMI (adjusted odds ratio 1.71 95% confidence interval 1.19 to 2.44), and the 1-year mortality rate was 18.9% versus 10.9%, respectively (hazard ratio 1.85, 95% confidence interval 1.41 to 2.43). From 1998 to 2006, an insignificant trend toward a 1-year mortality reduction among patients with recurrent STEMI was seen and those with a first STEMI had a significant mortality decrease. In conclusion, patients admitted for recurrent STEMI have worse in-hospital and 1-year outcomes that did not improve during the study period. An improved therapeutic approach is needed for these high-risk patients. [Copyright &y& Elsevier]

Abstract: Efimov physics in two nuclear-spin sublevels of bosonic lithium is studied and it is shown that the positions and widths of recombination minima and Efimov resonances are identical for both states within the experimental errors, which indicate that the short-range physics is nuclear-spin independent. We also find that the Efimov features are universally related across Feshbach resonances. These results crucially depend on careful mapping between the scattering length and the applied magnetic field which we achieve by characterization of the two broad Feshbach resonances in the different states by means of rf-spectroscopy of weakly bound molecules. By fitting the binding energies numerically with a coupled channels calculation we precisely determine the absolute positions of the Feshbach resonances and the values of the singlet and triplet scattering lengths. [Copyright &y& Elsevier]

Aims: The present study was designed to identify and compare predictors of short- and long-term mortality in elderly and young patients hospitalized with acute heart failure (HF). [ABSTRACT FROM PUBLISHER]

The predictive value of plasma atrial natriuretic peptide (ANP) on the cardioversion outcome was evaluated in 46 hospitalized patients with recent-onset atrial fibrillation (AF). Cardioversion was successful in 42 (91%) patients, 7 (15%) of them regained sinus rhythm spontaneously. After 12 months, 14 (33%) cardioverted patients were in chronic AF. There were no differences in plasma ANP levels between groups where cardioversion failed, those who cardioverted but later developed chronic AF or those who remained in sinus rhythm. However, among patients who were on antiarrhythmic therapy, ANP levels obtained after cardioversion were lower in those who later remained in sinus rhythm. We conclude that lower ANP after cardioversion may be associated with increased chances of long-term preservation of sinus rhythm.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

It is difficult to assess acute therapeutic intervention therapy, particularly in patients with unstable angina. Our aim was to evaluate the feasibility of a pain-scoring method and to compare the response to sublingual administration of an isosorbide dinitrate (ISDN) tablet, ISDN spray or nitroglycerin (NTG) spray. Pain scoring was assessed by the subjective grading of the patients’ pain severity from 1 to 10. We studied 205 patients (mean age 66 ± 13 years). Pain attenuation, defined as at least 50% reduction in pain intensity, occurred in the ISDN tablet, ISDN spray and NTG spray groups after 360 ± 290, 318 ± 289 and 233 ± 271 s, respectively (p = 0.0005). In conclusion, pain scoring is a feasible and useful clinical method to assess antianginal therapy in unstable angina patients. Sublingual nitrate sprays, particularly NTG, seem to alleviate anginal pain faster than ISDN tablets in this patient population. [ABSTRACT FROM AUTHOR]

Reviews reports on the use of angiotensin-converting enzyme inhibitors (ACE-I) during pregnancy to determine fetal complications. ACE inhibition as treatment for pregnancy-induced hypertension; Role of renin angiotensin in amniotic fluid secretion; Determination of direct effects of ACE-I on the fetus; Risks of ACE-I treatment during pregnancy.

Investigates the effect of beta-blocker therapy in patients with coronary artery disease in New York Heart Association (NYHA) classes I and II. Baseline clinical characteristics of patients with coronary artery disease and NYHA classes I and II; Mortality rate of patients in NYHA functional classes I and II in relation to treatment with beta-blockers.

Assesses the relations between cardiac arrhythmias in pregnant patients referred for evaluation of palpitations, dizziness and syncope. Absence of correlation between the incidence of both ventricular and atrial premature complexes; Higher number of simple and multifocal complexes in patients with palpitations, dizziness or syncope.

Background: Long non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources). Methods: INFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell proliferation and chemotherapeutic drug response. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiation. Finally, we established a mouse K562 leukemia xenograft model to determine whether SNHG6 KD attenuates tumor growth in vivo. Results: The INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regulated by hematopoiesis-associated transcription factors. SNHG6 KD reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenuated tumor growth in vivo. Conclusions: Our approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with roles in hematopoiesis and leukemia. Such approaches can be readily applied to identify novel targets for precision medicine. [ABSTRACT FROM AUTHOR]

Mortality and morbidity after acute myocardial infarction (AMI) is higher in diabetic than in nondiabetic patients. Angiotensin-converting enzyme (ACE) inhibitors have been shown to exert a beneficial effect after AMI. We sought to evaluate the association between treatment with ACE inhibitors and 1-year outcome after AMI in diabetic and nondiabetic patients in a national survey. The study population was drawn from a national survey conducted in all coronary care units operating in Israel during a 5-month period in 1996, and included 2,179 patients with AMI: 533 diabetics (24%), 322 of whom received ACE inhibitors (60%) and 211 who did not; and 1,646 nondiabetics, 805 of whom received ACE inhibitors and 841 who did not. In both groups of patients, those treated with ACE inhibitors were older, included more women, more had a history of AMI, anterior wall AMI, or hypertension, and more had worse Killip class on admission. Diabetic patients treated with ACE inhibitors experienced lower 1-year mortality rates than diabetics not treated with ACE inhibitors (16.2% vs 18.8%, respectively; covariate adjusted hazard ratio 0.47, 95% confidence interval 0.30 to 0.74). In nondiabetic patients, however, ACE inhibitor treatment was not associated with a better outcome (10.2% vs 7.3%, respectively; covariate adjusted hazard ratio 0.80; 95% confidence interval 0.56 to 1.15). Thus, treatment with ACE inhibitors after AMI appears to be particularly beneficial in diabetic patients. The beneficial effect observed supports the widespread use of ACE inhibitors in diabetic patients after AMI. [ABSTRACT FROM AUTHOR]

Present guidelines endorse complete removal of cardiovascular implantable electronic devices (pacemakers/defibrillators), including extraction of all intracardiac electrodes, not only for systemic infections, but also for localized pocket infections. The authors evaluated the efficacy of delivering continuous, in situ–targeted, ultrahigh concentration of antibiotics (CITA) into the infected subcutaneous device pocket, obviating the need for device/lead extraction. The CITA group consisted of 80 patients with pocket infection who were treated with CITA during 2007-2021. Of them, 9 patients declined lead extraction because of prohibitive operative risk, and 6 patients had questionable indications for extraction. The remaining 65 patients with pocket infection, who were eligible for extraction, but opted for CITA treatment, were compared with 81 patients with pocket infection and similar characteristics who underwent device/lead extraction as primary therapy. A total of 80 patients with pocket infection were treated with CITA during 2007-2021. CITA was curative in 85% (n = 68 of 80) of patients, who remained free of infection (median follow-up 3 years [IQR: 1.0-6.8 years]). In the case-control study of CITA vs device/lead extraction, cure rates were higher after device/lead extraction than after CITA (96.2% [n = 78 of 81] vs 84.6% [n = 55 of 65]; P = 0.027). However, rates of serious complications were also higher after extraction (n = 12 [14.8%] vs n = 1 [1.5%]; P = 0.005). All-cause 1-month and 1-year mortality were similar for CITA and device/lead extraction (0.0% vs 3.7%; P = 0.25 and 12.3% vs 13.6%; P = 1.00, respectively). Extraction was avoided in 90.8% (n = 59 of 65) of extraction-eligible patients treated with CITA. CITA is a safe and effective alternative for patients with pocket infection who are unsuitable or unwilling to undergo extraction. (Salvage of Infected Cardiovascular Implantable Electronic Devices [CIED] by Localized High-Dose Antibiotics; NCT01770067) [Display omitted] [Display omitted] [ABSTRACT FROM AUTHOR]

Beta-blockers are commonly used drugs during pregnancy, especially in women with heart disease, and are regarded as relatively safe although evidence is sparse. Differences between beta-blockers are not well-studied. In the Registry of Pregnancy And Cardiac disease (ROPAC, n = 5739), a prospective global registry of pregnancies in women with structural heart disease, perinatal outcomes (small for gestational age (SGA), birth weight, neonatal congenital heart disease (nCHD) and perinatal mortality) were compared between women with and without beta-blocker exposure, and between different beta-blockers. Multivariable regression analysis was used for the effect of beta-blockers on birth weight, SGA and nCHD (after adjustment for maternal and perinatal confounders). Beta-blockers were used in 875 (15.2%) ROPAC pregnancies, with metoprolol (n = 323, 37%) and bisoprolol (n = 261, 30%) being the most frequent. Women with beta-blocker exposure had more SGA infants (15.3% vs 9.3%, p < 0.001) and nCHD (4.7% vs 2.7%, p = 0.001). Perinatal mortality rates were not different (1.4% vs 1.9%, p = 0.272). The adjusted mean difference in birth weight was −177 g (−5.8%), the adjusted OR for SGA was 1.7 (95% CI 1.3–2.1) and for nCHD 2.3 (1.6–3.5). With metoprolol as reference, labetalol (0.2, 0.1–0.4) was the least likely to cause SGA, and atenolol (2.3, 1.1–4.9) the most. In women with heart disease an association was found between maternal beta-blocker use and perinatal outcomes. Labetalol seems to be associated with the lowest risk of developing SGA, while atenolol should be avoided. [Display omitted] • Beta-blocker use is independently associated with small for gestational age infants. • Labetalol has the lowest risk of small for gestational age and atenolol the highest. • Fetal growth scans are recommended in women using beta-blockers. • Women should be counselled about the benefits and risks of medication use. [ABSTRACT FROM AUTHOR]

Mortality and morbidity after acute myocardial infarction (AMI) is higher in diabetic than in nondiabetic patients. Angiotensin-converting enzyme (ACE) inhibitors have been shown to exert a beneficial effect after AMI. We sought to evaluate the association between treatment with ACE inhibitors and 1-year outcome after AMI in diabetic and nondiabetic patients in a national survey. The study population was drawn from a national survey conducted in all coronary care units operating in Israel during a 5-month period in 1996, and included 2,179 patients with AMI: 533 diabetics (24%), 322 of whom received ACE inhibitors (60%) and 211 who did not; and 1,646 nondiabetics, 805 of whom received ACE inhibitors and 841 who did not. In both groups of patients, those treated with ACE inhibitors were older, included more women, more had a history of AMI, anterior wall AMI, or hypertension, and more had worse Killip class on admission. Diabetic patients treated with ACE inhibitors experienced lower 1-year mortality rates than diabetics not treated with ACE inhibitors (16.2% vs 18.8%, respectively; covariate adjusted hazard ratio 0.47, 95% confidence interval 0.30 to 0.74). In nondiabetic patients, however, ACE inhibitor treatment was not associated with a better outcome (10.2% vs 7.3%, respectively; covariate adjusted hazard ratio 0.80; 95% confidence interval 0.56 to 1.15). Thus, treatment with ACE inhibitors after AMI appears to be particularly beneficial in diabetic patients. The beneficial effect observed supports the widespread use of ACE inhibitors in diabetic patients after AMI. [Copyright &y& Elsevier]

Phenylketonuria is characterized by the accumulation of phenylalanine, resulting in severe cognitive and neurological disorders if not treated by a remarkably strict diet. There are two approved drugs today, yet both provide only a partial solution. We have previously demonstrated the formation of amyloid-like toxic assemblies by aggregation of phenylalanine, suggesting a new therapeutic target to be further pursued. Moreover, we showed that compounds that halt the formation of these assemblies also prevent their resulting toxicity. Here, we performed high-throughput screening, searching for compounds with inhibitory effects on phenylalanine aggregation. Morin hydrate, one of the most promising hits revealed during the screen, was chosen to be tested in vivo using a phenylketonuria mouse model. Morin hydrate significantly improved cognitive and motor function with a reduction in the number of phenylalanine brain deposits. Moreover, while phenylalanine levels remained high, we observed a recovery in dopaminergic, adrenergic, and neuronal markers. To conclude, the ability of Morin hydrate to halt phenylalanine aggregation without reducing phenylalanine levels implies the toxic role of the phenylalanine assemblies in phenylketonuria and opens new avenues for disease-modifying treatment. [Display omitted] • Inborn error of metabolism disorders, such as phenylketonuria, have no disease-modifying treatment. • Amyloid etiology was suggested to play a key role in these disorders. • High throughput screening allowed the identification of potent inhibitors of phenylamine amyloid formation. • The lead inhibitor showed near completer recovery of cognitive and motoric activities of phenylketonuria model mice. • The work paves the way toward safe and efficient treatment of phenylketonuria. [ABSTRACT FROM AUTHOR]

Background: The treatment of myopericarditis is different than that of acute myocardial infarction (AMI). However, since their clinical presentation is frequently similar it may be difficult to distinguish between these entities despite a disparate underlying pathogenesis. Myopericarditis is primarily an inflammatory disease associated with high C-reactive protein (CRP) and relatively low elevated troponin concentrations, while AMI is characterized by the opposite. We hypothesized that evaluation of the CRP/troponin ratio on presentation to the emergency department could improve the differentiation between these two related clinical entities whose therapy is different. Such differentiation should facilitate triage to appropriate and expeditious therapy. Methods: We evaluated the CRP/troponin ratio on presentation among patients consecutively included in a large single center registry that included 1898 consecutive patients comprising 1025 ST-elevation myocardial infarction (STEMI) patients, 518 Non-STEMI (NSTEMI) patients, and 355 patients diagnosed on discharge as myopericarditis. CRP and troponin were sampled on admission in all patients and their ratio was assessed against discharge diagnosis. ROC analysis of the CRP/troponin ratios evaluated the diagnostic accuracy of myopericarditis against all AMI, STEMI, and NSTEMI patients. Results: Median admission CRP/troponin ratios were 84, 65, and 436 mg×ml/liter×ng in STEMI, NSTEMI and myopericarditis groups, respectively (p<0.001) demonstrating good differentiating capability. The Receiver-operator-curve of admission CRP/troponin ratio for diagnosis of myopericarditis against all AMI, STEMI, and NSTEMI patients yielded an area-under-the curve of 0.74, 0.73, and 0.765, respectively. CRP/troponin ratio>500 resulted in specificity exceeding 85%, and for a ratio>1000, specificity>92%. Conclusion: The CRP/troponin ratio can serve as an effective tool to differentiate between myopericarditis and AMI. In the appropriate clinical context, the CRP/troponin ratio may preclude further evaluation. [ABSTRACT FROM AUTHOR]

Abstract: We report on the experimental observation of dynamical collapses which address selectively the TM-mode of a laser subject to optical feedback with variably rotated polarization. Simultaneously, the TE-mode which remains the dominant lasing mode exhibits power bursts. We analyze the relative phase shift between the feedback fields into the TE- and TM-mode and find that the dynamical collapses, observed in a specific range of polarization rotation angles, can be attributed to large phase shift feedback conditions applied on the TM-mode. [Copyright &y& Elsevier]

Objectives To describe the incidence, onset, predictors and outcome of ventricular tachyarrhythmia (VTA) in pregnant women with heart disease. Background VTA during pregnancy will cause maternal morbidity and even mortality and will have impact on fetal outcome. Insufficient data exist on the incidence and outcome of VTA in pregnancy. Methods and results From January 2007 up to October 2013, 99 hospitals in 39 countries enrolled 2966 pregnancies in women with structural heart disease. Forty-two women (1.4%) developed clinically relevant VTA during pregnancy, which occurred mainly in the third trimester (48%). NYHA class > 1 before pregnancy was an independent predictor for VTA. Heart failure during pregnancy was more common in women with VTA than in women without VTA (24% vs. 12%, p = 0.03) and maternal mortality was respectively 2.4% and 0.3% (p = 0.15). More women with VTA delivered by Cesarean section than women without VTA (68% vs. 47%, p = 0.01). Neonatal death, preterm birth (< 37 weeks), low birthweight (< 2500 g) and Apgar score < 7 occurred more often in women with VTA (4.8% vs. 0.3%, p = 0.01; 36% vs. 16%, p = 0.001; 33% vs. 15%, p = 0.001 and 25% vs. 7.3%, p = 0.001, respectively). Conclusions VTA occurred in 1.4% of pregnant women with cardiovascular disease, mainly in the third trimester, and was associated with heart failure during pregnancy. NYHA class before pregnancy was predictive. VTA during pregnancy had clear impact on fetal outcome. [ABSTRACT FROM AUTHOR]

Objectives: We present our experience with a novel method for real time co-registration of intravascular ultrasound (IVUS) and coronary angiography. Background: A major limitation of the current practice of concomitant use of coronary angiography and IVUS is that the locations of the acquired IVUS images are not correlated with their exact locations on the vessel roadmap obtained by coronary angiography. Methods: Phantoms simulating the coronary tree were used to test the accuracy and potential of co-registration. Subsequently we examined patients who underwent IVUS during cardiac catheterization. Analysis and feasibility were performed in 42 arteries of 36 patients. Results: The statistical validation in phantoms resulted in a co-registration accuracy of 1.12 mm. The length measurement on an angiogram resulted in an accuracy of 0.38 mm. Co-registration in patients was successful in all cases and four categories were assisted by 1(bad) to 5 (good) grading. Accuracy (the co-registration precision in pointing at the exact corresponding location): 4.8±0.41; Ease of use and workflow: 4.74±0.44; Stent landing zone detection and evaluation: 4.58±0.5; Stent landing zone length and diameter measurement: 4.94±0.23. The co-registration error was estimated as no more than 1 mm. Conclusion: In this pilot study, we found that the novel IVUS and coronary angiography co-registration method is accurate, easy to use, fast and user-friendly. This method precludes the need to use motorized automated pull back device. [ABSTRACT FROM AUTHOR]

Background Stent thrombosis is a clinically significant event occurring days to weeks or, infrequently, months or years after percutaneous coronary intervention (PCI). Current therapeutic approach is immediate PCI aimed to recanalize the occluded artery in order to restore flow and diminish irreversible myocardial damage. Methods We evaluated the coronary patency, TIMI flow and TIMI myocardial perfusion grade (TMPG) in 6 patients presenting with STEMI due to stent thrombosis treated by thrombolysis followed by immediate PCI. These were compared with control patients treated conventionally by primary PCI. Results Immediate or early coronary angiography in the treatment group showed good coronary flow in 5 of 6 implicated arteries, whereas immediate angiography in the control group demonstrated 8 completely occluded coronary arteries of 9 with stent thrombosis. The pre-intervention TIMI flow in the control study group was 0.2 ± 0.5 (median–0), and TMPG was 0.1 ± 0.3 (median–0) compared with 2.1 ± 1.1 (median–2.3, p < 0.001) and 1.8 ± 1.0 (median–2, p < 0.001) in the treatment group, respectively. This striking difference in the rate of coronary patency, pre-procedural TIMI flow and TMPG, however, did not translate into better cardiac function in the treatment group. Conclusions These findings suggest that thrombolysis-facilitated PCI may confer benefit and need not be considered contraindicated when treating stent thrombosis. This therapeutic approach should be evaluated as a viable therapeutic approach to stent thrombosis. [ABSTRACT FROM AUTHOR]

Collaterals to occluded coronary arteries have been observed early after the onset of acute myocardial infarction (AMI). The pressure distal to the occluded segment of the culprit coronary artery (Pd) is generated by collateral flow from the feeding coronary artery supplied by the systemic circulation. The aim of the study was to assess the relation between systemic blood pressure (BP) and Pd. Systemic BP and Pd were measured simultaneously during intervention of totally occluded coronary arteries in 152 patients admitted for AMI. Patients were divided into groups by time from symptom onset to Pd measurement. There was a significant positive correlation between Pd and the systolic, diastolic, and mean BPs measured during the first 3 hours from symptom onset (n = 60; p <0.05, p <0.006, and p <0.005, respectively), from 3 to 12 hours (n = 56; p <0.02 for all), and >12 hours after symptom onset (n = 36; p <0.003 for all). The collateral flow, represented by calculated collateral flow index (mean 0.37 ± 0.14, median 0.36), was correlated with mean BP (p=0.05) but not with diastolic or systolic BP (p=NS) in the overall study population. Adirect relation was established during AMI between systemic BP and Pd at all time intervals from symptom onset. Collateral flow index correlated with mean BPand was strongly associated with Pd at all time intervals. In conclusion, the relation between Pd and systemic BP suggests caution when administering therapy that may lower systemic BP during AMI before restoring flow in the occluded culprit artery, as it may compromise collateral pressure and exacerbate myocardial ischemia. [ABSTRACT FROM AUTHOR]

Background: By and large, prior registries and randomized trials have not distinguished between acute heart failure (AHF) associated with acute coronary syndrome (ACS) versus other causes. Aims: To examine whether the treatments and outcomes of ACS-associated AHF are different from non-ACS-associated AHF. Methods: We examined in a prospective, nationwide hospital-based survey the adjusted outcomes of AHF patients with and without ACS as its principal cause. Results: Of the 4102 patients in our national heart failure survey, 2336 (56.9%) had AHF, of whom 923 (39.5%) had ACS-associated AHF. These patients were more likely to receive intravenous inotropes and vasodilators and to undergo coronary angiography and revascularization, but less likely to receive intravenous diuretics. The unadjusted in-hospital, 30-day, one-year, and four-year mortality rates for AHF patients with or without ACS were 6.5% versus 5.0% ( P == 0.13), 10.3% versus 7.5% ( P == 0.02), 26.6% versus 31.0% ( P == 0.02), and 55.3% versus 63.3% ( P == 0.0001), respectively. In the multivariate analysis, the adjusted mortality risk for patients with ACS at the respective time points were 1.46 (0.99--2.10), 1.67 (1.22--2.30), 1.02 (0.86--1.20), and 0.93 (0.82--1.04). Conclusions: Patients with ACS-associated AHF seem to have a unique clinical course and perhaps should be distinguished from other AHF patients in future trials and registries. [ABSTRACT FROM AUTHOR]

Background: Current guidelines regarding the use of intravenous morphine (IM) in the management of patients with acute decompensated heart failure (ADHF) are discordant; whereas the American guidelines reserve IM for terminal patients, the European guidelines recommend its use in the early stage of treatment. Our aim was to determine the impact of IM on outcomes of ADHF patients. Methods: Stepwise logistic regression and propensity score analysis of ADHF patients with and without use of IM was performed in a national heart failure survey. Results: Of the 4102 enrolled patients, we identified 2336 ADHF patients, of whom 218 (9.3%) received IM. IM patients were more likely to have acute coronary syndromes, acute rather than exacerbation of chronic heart failure, and diabetes mellitus and dyslipidemia. They had higher heart rate, were less likely to receive diuretics and more likely to receive aspirin and statins. Unadjusted in-hospital mortality rates were 11.5% versus 5.0% for patients who did or did not receive IM, and the adjusted odds ratio (OR) for in-hospital death was: 2.0 (1.1--3.5, P == 0.02). Using propensity analysis, we identified 218 matched pairs of patients who did or did not receive IM. In multivariable analysis accounting for the propensity score (c-statistic 0.82), IM was not associated with increased in-hospital death (OR: 1.2 (0.6--2.4), P == 0.55). Conclusion: IM was used sparingly in our ADHF cohort, and was independently associated with increased in-hospital death in multivariable analysis, but not in propensity score analysis. Thus, IM may be used in ADHF, but with caution. Further randomized trials are warranted. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess age differences in the utilization of class-I treatment guidelines and its effect on mortality in patients with ST-elevation myocardial infarction (STEMI). The study included 1026 consecutive patients from the prospective nationwide Acute Coronary Syndrome Israeli Survey (ACSIS). Primary reperfusion was used less often among elderly (age>75 years) patients than among those aged 65–74 and <65 years (46%, 63%, 64%, respectively, p (for trend)=0.004). Class-I evidence-based medications (EBM) at discharge (aspirin, β-blockers, angiotensin converting-enzyme inhibitors=ACEI, angiotensin receptor-blockers=ARBs and statins) were less frequently prescribed to elderly compared to younger age-subgroup (44%, 61%, 57%, respectively; adjusted odds ratio (OR)=0.62; 0.40–0.97 for age≥75 vs. age<65 years). Early and 1-year mortality rates were 3–5-fold higher among the elderly compared to patients <65 years. In the entire cohort use of primary reperfusion was associated with lower 1-year mortality (OR=0.69; 0.47–1.01), as was the use of EBM (OR=0.26; 0.17–0.41). These effects were similar across all age-subgroups but with a greater impact among the elderly, as the number of patients needed to treat (NNT) was significantly lower with advancing age. Better adherence to treatment guidelines may improve the prognosis of elderly patients with STEMI. [Copyright &y& Elsevier]

The article provides information on the mechanism of sudden death in the Wolff-Parkinson-White (WPW) syndrome. Sudden death is a rare complication of the WPW syndrome. This complication may occur without any apparent environmental triggers in young, previously asymptomatic persons. It is generally believed that the common mechanism of sudden death in WPW patients, especially in the young, is ventricular fibrillation precipitated by atrial fibrillation capable to conduct rapidly over the accessory pathway.

An abstract of the study "The Benefit of Early Use of Lipid-lowering Drugs at Discharge in Patients with Acute Coronary Syndromes and Heart Failure," by S. Gottlieb and J. Leor, is presented.

The adjustment of medications and dosages to the needs of individual patients with heart failure is mostly intuitive, but even when their effect on global myocardial function is measured by classic indexes, their effect on segmental function is overlooked. This study was conducted to assess the feasibility of using echocardiographic myocardial strain imaging to evaluate the effect of medication on global and segmental function in 21 ambulatory patients with heart failure (mean age 65 ± 11 years) who had echocardiographic studies performed before and 2 hours after ingesting their regular morning medications. The ejection fraction, global and regional strain, and time to regional peak strain were compared between the 2 examinations. Medication induced no significant changes in mean ejection fraction (28.6 ± 7.8% to 27.5 ± 9.9%) and mean global strain (−9.5 ± 3.6% to −9.8 ± 3.2%). Changes in segmental strain depended on baseline function: normal segments (peak strain more negative than −12%) deteriorated (−15.5 ± 2.7% to −13.7 ± 4.6%, p <0.0001), but dysfunctional segments (peak strain less negative than −8%) improved (−5.3 ± 2.0% to −7.4 ± 4.3%, p <0.0001). Medication also improved segmental synchronization: average time to peak strain of segments in which peak strain was attained before aortic valve closure increased (325 ± 69 to 375 ± 100 ms, p <0.0001), but that of segments with postsystolic shortening at baseline decreased (451 ± 93 to 435 ± 93 ms, p <0.006). Thus, the time interval between time to peak strain of segments with systolic and post-systolic shortening at baseline was halved after medication. In conclusion, medications for heart failure induced an increase in the echocardiographically determined peak strain of myocardial segments with impaired function at baseline but decreased the peak strain of normally contracting segments. Medications also improved the synchronization of myocardial contraction. Neither the global ejection fraction nor global strain reflected these changes. Thus, medication tended to improve the homogeneity of left ventricular contraction. [Copyright &y& Elsevier]

The article focuses on the study of the association of admission glucose levels and mortality among hospitalized nondiabetic patients with heart failure. The authors studied the data of 4,102 patients where it centers on the 1,122 nondiabetic patients who were admitted because of acute or chronic HF. The result of the study showed that in-hospital and 60-day mortality are associated with admission blood glucose levels but not the 6-month or 1-year mortality in nondiabetic patients with HF.

Abstract: Background: Acute heart failure (AHF) evolves through two phases. In the first phase, there is interstitial congestion with no clinical sign of edema (preclinical phase); the second, during which lung alveoli begin to fill with fluid, manifests as clinically overt alveolar edema. Treatment of AHF at its preclinical phase can alleviate its clinical impact. Presently, there is no technique that detects the interstitial phase of AHF. We used a device based on a new method of lung bioimpedance measurement. The device measures internal thoracic impedance (ITI), which nearly equals inherent lung bioimpedance. This method can detect small changes in lung fluid that occur during the interstitial stage of AHF. Aim: The objective of this study was to assess the feasibility and efficacy of the said new method in detecting preclinical AHF. Methods: Internal thoracic impedance and pertinent clinical parameters were monitored for 72 h in 403 patients hospitalized for an acute coronary syndrome without evidence of AHF at study entry. Results: Seventy patients developed AHF during monitoring. Internal thoracic impedance decreased in these patients by 16.4% (95% CI=−12.2% to −20.6%; P<.0001) from the baseline level at 44±15.1 min prior to the onset of lung rales. The other 333 patients had no clinical sign of AHF, and their ITI declined only by 4.5% (95% CI=2.5% to −11.5%; P=.3) compared with the baseline level. Conclusion: The new method for ITI measurement is sufficiently sensitive in detecting AHF at its preclinical stage. An ITI decrease of more than 12% heralds the appearance of clinically overt AHF and, thus, allows earlier therapy. [Copyright &y& Elsevier]

One hundred thirty-nine patients who underwent transesophageal echocardiographic studies were grouped by their maximal left atrial (LA) volumes, and their stroke volumes, emptying fractions, and fractional shortening were calculated. In large atria, an inverse relation was found between further increases in LA volume and LA function, determined by emptying fractions and fractional shortening. [Copyright &y& Elsevier]

Background: Cigarette smoking is a known risk factor for sudden cardiac death (SCD). However, the effect of continued cigarette smoking and smoking cessation on SCD risk in patients with established coronary artery disease (CAD) is subject to controversy. We, therefore, evaluated the effect of cigarette smoking on SCD risk in a large cohort of patients with established CAD. Methods: The study population was composed of 3122 patients with a previous myocardial infarction or stable angina who participated in the Bezafibrate Infarction Prevention Trial. Patients were prospectively followed up for a mean of 8.2 years. The primary end point was the incidence of SCD according to smoking status. Results: Among the 370 patients who were current smokers, 30 (8.1%) experienced SCD; 83 (4.6%) of the 1821 patients who had quit smoking and 43 (4.6%) of the 931 patients who had never smoked experienced SCD (P = .01). In multivariate analyses, current smoking was associated with a significant increase in the risk of SCD (hazard ratio, 2.47; 95% confidence interval, 1.46-4.19). Patients who had stopped smoking had no significant increase in the risk of SCD compared with patients who had never smoked (hazard ratio, 1.06; 95% confidence interval, 0.70-1.62). Conclusions: Current cigarette smoking is a powerful independent predictor of SCD risk in patients with CAD. Patients who quit smoking experienced a significant reduction in SCD risk. Thus, efforts to reduce mortality from SCD in patients with CAD should include vigorous smoking cessation strategies. [ABSTRACT FROM AUTHOR]

: PurposeLittle is known about the advantages and disadvantages of participation in a clinical trial for patients with coronary heart disease. We hypothesized that participation itself in a long-term clinical trial with regular clinical evaluation and adjustment of treatments might lead to survival gain among patients with coronary artery disease who agreed or refused to participate in the Bezafibrate Infarction Prevention study.: Subjects and methodsThe study was performed in 18 university hospitals. There were 3502 patients who fulfilled the inclusion criteria. Among them, 3122 patients signed informed consent and were included in the study (“participants”), whereas 380 declined to participate (“nonparticipants”). For all participants, routine visits to the clinics were scheduled bimonthly for study medication distribution and compliance assessment, and every 4 months for clinical evaluation and management. Nonparticipants continued with community-based treatment and were followed only for mortality.: ResultsThe two groups were similar with regard to age, sex, and the prevalence of most cardiovascular diseases, risk factors, and medications, except that participants were more likely to have presented with an anginal syndrome (1788 [57%] vs. 190 [50%]) and to have symptomatic heart failure (754 [25%] vs. 66 [18%]). During follow-up (mean [± SD], 7.7 ± 0.8 years), 475 patients died. All-cause mortality was similar in participants (n = 423 [13.6%]) and nonparticipants (n = 52 [13.7%]). In a multivariate analysis, participation in the clinical trial was not associated with all-cause mortality (hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.70 to 1.30) or cardiac mortality (HR = 1.12; 95% CI: 0.72 to 1.74).: ConclusionParticipation in a long-term clinical trial in a country with readily accessible community-based medicine may not lead to survival gain in patients with coronary artery disease. [Copyright &y& Elsevier]

Few data are available regarding the prevalence and prognostic significance of the triple coexistence of undiagnosed systemic hypertension, diabetes mellitus, and coronary heart disease. This study aimed to evaluate the prevalence and prognostic significance of unrecognized hypertension in cardiac diabetic patients previously defined as "normotensives" over a 5-year follow-up period. The study sample comprised 11,515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who were screened but not included in the Bezafibrate Infarction Prevention study. Among them, 9,033 were nondiabetics and 2,482, diabetics. The diabetics were divided into 3 groups: (1) 1,272 normotensives, (2) 152 patients without history of hypertension but with elevated blood pressure ("unrecognized hypertensives"), and (3) 1,058 hypertensives with established diagnosis. The prevalence of both diagnosed and unrecognized hypertension in diabetics pooled together increased from 49% to 69% when World Health Organization and new Joint National Committee-VI criteria were compared. Crude all-cause mortality was lower in nondiabetics than in diabetics (11.2% vs 22.0%; p <0.001). Among diabetics the lowest all-cause mortality was documented for normotensives (19.3%), whereas the highest mortality was observed in unrecognized hypertensives (26.3%, p = 0.003). Both unrecognized and established hypertensives demonstrated a significant stroke-related mortality excess: about four- and threefold increases in cerebrovascular accident-related death, respectively, were observed (p = 0.002). On multivariate analysis, both unrecognized and diagnosed hypertension were consistent predictors of increased all-cause mortality, with a hazard ratio of 1.28 (95% confidence interval 0.90 to 1.82) and 1.24 (95% confidence interval 1.03 to 1.49), respectively. Our findings demonstrate widespread undiagnosed hypertension in diabetic coronary patients; their 5-year mortality was significantly increased compared with normotensives, and tended to be even higher than in diabetics previously identified as hypertensives. [ABSTRACT FROM AUTHOR]

Patients with chronic CAD and a history of cerebrovascular events were compared with patients without prior cerebrovascular events to assess the effect of these events on 5-year prognosis. Despite adjustment for older age and higher comorbidity among patients who had experienced a cerebrovascular event, a history of such an event was associated with an increased risk of 1.86 for total mortality. [ABSTRACT FROM AUTHOR]