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Aims Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. Methods and results We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66–75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02–1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10–1.30; P Conclusion Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization.

BACKGROUND Treatment of patients with acute myocardial infarction should aim to restore blood flow in the infarct-related artery as soon as possible. Thrombolytic therapy has recently been compared with direct angioplasty; however, these interventions may not be sufficient, and coronary artery bypass grafting (CABG) may be necessary. METHODS In a series of 301 patients with acute myocardial infarction, randomly assigned either to receive intravenous streptokinase (n = 149) or to undergo percutaneous transluminal coronary angioplasty (PTCA; n = 152), 31 patients (aged 61 +/- 10 years; 27 men, four women) underwent CABG within 6 weeks of acute myocardial infarction. RESULTS Twelve patients (nine in the PTCA group and three in the streptokinase group) underwent surgery within 48 h of the onset of symptoms. Bypass surgery was performed in the streptokinase group on failure of thrombolytic therapy (n = 2), recurrent ischemia (n = 4), or postinfarct angina (n = 9). In the PTCA group, CABG was performed for left main stenosis (n = 6), failed PTCA (n = 3), recurrent ischemia (n = 2), or postinfarct angina (n = 5). An intra-aortic balloon pump (IABP) was required in 15 patients (five streptokinase and 10 PTCA). Major complications after CABG were more common among patients who underwent surgery within 48 h than those after 48 h (eight in 12 patients versus four in 19, respectively). After 17.0 +/- 8.6 months (range 3-33 months), two patients had died; one of end-stage heart failure after 3 months, and one of a stroke after 16 months (both were in the PTCA group and one had undergone surgery within 48 h). One patient suffered a reinfarction after 11 months and one a non-fatal stroke after 1 month (both underwent CABG within 48 h). The left ventricular ejection fraction did not differ between the groups (43 +/- 15% for the 'early' group and 42 +/- 11% for the 'late' group). CONCLUSION CABG can be performed safely and effectively after initial treatment with direct angioplasty or thrombolytic therapy after acute myocardial infarction. If it is performed within 48 h of onset of symptoms, (in-hospital) morbidity is higher, without affecting mortality or left ventricular function.

Objective Repeated left ventricular ejection fraction (LVEF) analyses with sequential single-dose radionuclide ventriculography might be an interesting technique for monitoring the effect of positive inotropic interventions. The aim of the study was to assess the reproducibility of LVEF measurement with planar radionuclide ventriculography within 3 h, using a standard single dose of radioactive tracer. Methods Sixteen patients underwent routine planar radionuclide ventriculography with a standard dose of 500 MBq of [[Tc-99m]pertechnetate and returned after 3 h for a repeat planar radionuclide ventriculography without administration of additional tracer. Results The average initial LVEF was 35.1 +/- 18.6%-point (range, 12%-point to 68%-point). The mean difference of the LVEF between the initial planar radionuclide ventriculography and the repeat planar radionuclide ventriculography was 2.8% +/- 6.3% (range, - 11.8% to 13.3%, P= NS). The correlation between both measurements was significant with a correlation coefficient of 0.995 (P Conclusion Repeated radionuclide ventriculography with a 3 h interval using a single standard dose of 500 MBq of [Tc-99m]pertechnetate is highly reproducible and will be useful for monitoring the effect of positive inotropic interventions.

Background - Intracoronary flow and pressure measurements can be used for evaluating intermediate lesions. Studies focussing on short- and medium-term results demonstrated its safety. Longterm results are, however, not available. Objective - The goal of this study was to assess the long-term safety and clinical implications of decision making for intermediate coronary stenosis based on intra-coronary haemodynamic measurements. Methods and results - In this prospective study, 61 patients with an intermediate coronary stenosis were included between January 1994 and December 1998. In these patients either coronary flow reserve or fractional flow reserve was measured. Death, target vessel revascularization, myocardial infarction, unstable angina and cerebrovascular accident were considered as major adverse cardiac events. The patients were followed during 5.5 (1.8) years for the occurrence of major adverse cardiac events (MACE).Although many patients presented with complaints, only 19.7% experienced a MACE in the follow-up period. Conclusion - Intracoronary measurements of CFR and FFR can be routinely used for objective clinical decision making in intermediate coronary stenoses. The low 5-year event rate supports conservative treatment strategy when cut-off values are implemented.

The purpose of this study was to appraise the value of PET in the assessment of the effect of supposedly proangiogenic new therapies such as gene therapy with vascular endothelial growth factor (VEGF) gene and endomyocardial laser therapy. Methods: Thirty-five patients with end-stage coronary artery disease and class III (Canadian Cardiovascular Society) angina were included. Myocardial ischemia was evaluated with dipyridamole PET scanning and exercise tolerance with bicycle ergometry. Ten patients were treated with naked plasmid DNA encoding for human VEGF(165) (VEGF) and 12 patients were treated with laser therapy (direct myocardial revascularization [DMR]) using an electromechanical mapping system. Thirteen patients were treated with standard medical therapy (control). Results: In both active treatment groups, angina was reduced in most subjects, except in 2 VEGF and 5 DMR patients. In the control group, no improvement in anginal classification was found, except in 3 subjects. On the PET scan, solely in the VEGF group, the stress perfusion was significantly improved (from 57 +/- 33 to 81 +/- 55 mL/min/100 g; P = 0.031). Furthermore, in the VEGF group, the number of ischemic segments was reduced from 274 +/- 41 to 234 +/- 48 segments (P = 0.004) but not in the DMR group (from 209 +/- 43 to 215 +/- 52 segments) or in the control group (from 218 +/- 18 to 213 +/- 28 segments). Bicycle exercise duration showed slight nonsignificant changes in the VEGF group (from 3.6 +/- 2.0 to 4.6 +/- 2.1 min), in the DMR group (from 5.1 +/- 1.5 to 4.7 +/- 1.3 min), and in the control group (from 3.3 +/- 1.8 to 3.5 +/- 2.3 min). Conclusion: PET showed that intramyocardial gene therapy with the human VEGF(165) gene in contrast to laser DMR treatment effectively reduces myocardial ischemia.

Patients with heart failure have, in spite of improved palliative therapies, bad prognosis. Cardiac tissue engineering by use of a temporary bioscaffold and cardiomyocytes may help to find answers for future treatments in heart failure. For that purpose two neonatal rat heart ventricular cell fractions were obtained after a gradient cell separation. Time related characteristics of Fractions I and 11 were established in two-dimensional (2-D) and three-dimensional (3-D) cell cultures. The 3-D cardiac constructs were obtained by use of a bovine type I collagen matrix after culturing either under static conditions or in the HARV bioreactor. With the 2-D cultures contracting cells were present after 1 day, and reached confluency from day 5 on and this was maintained up to 135 days. In Fraction-I some non-contracting cells were always noticed between the (in time in unison) contracting cells. Transmission electron microscopy (TEM) revealed that these mainly concerned fibroblasts. Differences in the expression of alpha-SM-1 actin and troponin-T were observed between the two fractions. In both fractions endothelial cells and macrophages were only sporadically observed. All through the 3-D matrix pendant-like single cell and clustered cell contractions were present after 1-2 days, resulting in time in unison contracting of cells with the collagen matrices. The whole event was faster with Fraction-I and was observed up to 3 weeks. At this time point clusters of troponin-T positive cells were found scattered through the collagen matrices. Additionally, TEM revealed healthy layers of connected cardiomyocytes with intercalated discs, in this case on and in between the collagen fibres. These findings provide evidence that in unison contracting structurally organized cell-matrix cardiac constructs can be engineered by use of co-cultures (neonatal cardiomyocytes and fibroblasts) and collagen matrices, which is very promising for the repair of larger scar areas of the myocardium. (C) 2002 Elsevier Science Ltd. All rights reserved.

Intracoronary-derived, pressure-based fractional flow reserve (FFR) is important for clinical decision-making in patients with 1-vessel coronary artery disease (CAD). In the present study, we investigated the prognostic value of FFR in patients with intermediate stenoses and multivessel CAD. Therefore, we analyzed 107 patients with stable angina pectoris who underwent myocardial perfusion scintigraphy and showed no perfusion defects in the region of the intermediate lesion. At angiography, FFR was determined distal to the intermediate lesion. FFR was abnormal (i.e.

Background: Endothelial dysfunction is useful in predicting future cardiovascular disease. At present several tests are available to test endothelial function: coronary diameter response to acetylcholine, forearm bloodflow (FBF) response to acetylcholine, and brachial artery flow-mediated dilative (FMD) response to postischemic hyperemia. This study aimed to compare the three most frequently reported endothelial function tests. Methods: Twenty-eight patients (19 males and nine females, mean age 57 years) referred for diagnostic coronary angiography were considered for endothelial function measurement in the coronary artery as well as in the forearm by FBF and FMD. Results: Acetylcholine decreased the mean coronary diameter by 7.4% (SD 6.3%) and increased the mean FBF by 230% (SD 152%). Hyperemia increased the mean brachial diameter by 6.7% (SD 4.8%). The effect of acetylcholine on forearm resistance vessels was significantly related to the effect of acetylcholine on the coronary conduit vessels (P=0.039). Nonetheless, FMD was not related to FBF nor to the coronary response. Conclusion: In patients with mild coronary endothelial dysfunction, forearm vasoreactivity is related to the coronary response, provided that the same stimulus is used.

Aim: Autonomic impairment is related to the incidence of sudden death in chronic heart failure (CHF). Our objective was to study autonomic profiles in patients with mild CHF due to coronary artery disease, and to investigate the value of add-on P-blockade. Methods and results: Measures of autonomic function (plasma norepinephrine, heart rate [HR] variability, autonomic function testing), and exercise capacity, were compared between 24 patients with mild CHF, and 24 healthy controls. In this mechanistic study, we assessed the effect of 26 weeks metoprolol treatment in a double-blind, randomized, placebo-controlled design. All patients received metoprolol sustained release (200 mg; n = 12) or placebo (n = 12). Assessments were made at baseline and after 10 and 26 weeks' treatment. At baseline, norepinephrine levels were elevated, while HR variability parameters were decreased in patients vs. controls (both P

Background-Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that regulates expression of genes involved in O-2 homeostasis, including vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis. We sought to exploit this native adaptive response to hypoxia as a treatment for chronic ischemia. Methods and Results-A hybrid protein consisting of DNA-binding and dimerization domains from the HIF-1 alpha subunit and the transactivation domain from herpes simplex virus VP16 protein was constructed to create a strong, constitutive transcriptional activator. After transfection into HeLa, C6, and Hep3B cells, this chimeric transcription factor was shown to activate expression of the endogenous VEGF gene, as well as several other HIF-1 target genes in vitro. The bioactivity of HIF-1 alpha /VP16 hybrid gene transfer in vivo was examined in a rabbit model of hindlimb ischemia. Administration of HIF-1 alpha /VP16 was associated with significant improvements in calf blood pressure ratio, angiographic score, resting and maximal regional blood flow, and capillary density (all P Conclusions-The HIF-1/VP16 hybrid transcription factor is able to promote significant improvement in perfusion of an ischemic limb. These results confirm the feasibility of a novel approach for therapeutic angiogenesis in which neovascularization may be achieved indirectly by use of a transcriptional regulatory strategy.

1 We evaluated the role of SH-groups in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. To this end, we compared the vasoprotective effect of chronic treatment with zofenopril (plus SH-group) versus lisinopril (no SH-group), or N-acetylcysteine (only SH-group) in myocardial infarcted (MI) heart failure rats. 2 After 11 weeks of treatment, aortas were obtained and studied as ring preparations for endothelium-dependent and -independent dilatation in continuous presence of indomethacin to avoid interference of vasoactive prostanoids, and the selective presence of the NOS-inhibitor L-NMMA to determine NO-contribution. 3 Total dilatation after receptor-dependent stimulation with acetylcholine (ACh) was attenuated (-49%, P

The cold face test has been found to be a simple clinical test to elicit the diving reflex, which assesses function of the sympathetic and parasympathetic nerve systems at the same time. However, there is no consensus about how the test should be performed without confounding the results by eliciting other reflexes, such as the oculocardiac reflex. The object of this study was to compare and standardize methods for per forming the cold face test. Reproducibility of results was assessed. Groups of 6 to 11 subjects participated in each protocol. To act as a cold stimulus a bag filled with iced-water and having a wet surface was used. The effects of allowing breathing to continue, of different masses of the bag, and of avoiding ocular pressure by wearing diving goggles were investigated. Blood pressure and heart rate were measured beat to beat using an automatic blood pressure measuring device. The cold stimulus used in this study was too small to elicit the oculocardiac reflex: wearing diving goggles and different masses of the bag had no influence on the response. The prevention of breathing, however, tended to enhance the fall ill heart rate during the cold stress. Reproducibility was highest when the subjects were habituated to the intensity of the stimulus. We recommend practising the test method in advance and performing it in a setting where the subject is unable to breathe.

The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. in the control group, SCS was switched off during 4 weeks before the end of the study. The control group had no crossover period. Measurements were done at baseline, then after 4 and 8 weeks. The first periods at 4 weeks of each sequence of both groups were compared. In addition, a comparison of clinical variables was pet-formed between the study group 4 weeks after withholding stimulation and the control group 4 weeks following randomization. A total number of 24 patients with refractory angina and an implanted spinal cord stimulator were included in the study (n = 12) and control group. Angina pectoris complaints, nitroglycerin intake, ischemia, and heart rare variability using 48-hour ambulatory electrocardiographic monitoring were assessed. In addition, neurohormonal status and symptom-limited aerobic capacity were evaluated. There was no increase of anginal complaints or ischemia after withholding stimulation. Neurohormonal levels and aerobic capacity were not altered. We conclude that there is no adverse clinical rebound phenomenon after withholding neurostimulation in patients with refractory angina pectoris.

Chlamydia pneumoniae is frequently found in atherosclerotic lesions, and high titers of specific antibodies are associated with increased risk for acute myocardial infarction, However, a causative relation has not been established yet. We performed a prospective study of 93 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) to investigate whether angioplasty influences Chlamydia-specific antibody titers and whether there is an association with restenosis, Blood samples were obtained before and 1 and 6 months after angioplasty, Antibodies against chlamydial lipopolysaccharide and against purified C. pneumoniae elementary bodies were measured by enzyme-linked immunosorbent assay (ELISA). After angioplasty, the prevalence of antibodies to lipopolysaccharide rose from 20 to 26% for immunoglobulin A (IgA), from 53 to 64% for IgG, and from 2 to 7% for IgM (P = 0.021, 0.004, and 0.046, respectively). There was a rapid increase of mean antibody titers of all antibody classes within 1 month of PTCA, During the following 5 months, antibody titers decreased slightly but were still higher than baseline values. Results of the C. pneumoniae-specific ELISA were essentially the same. The rise of anti-Chlamydia antibodies was not caused by unspecific reactivation of the immune system, as levels of antibodies against cytomegalovirus did not change. Neither seropositivity nor antibody titers were related to restenosis. However, increases in mean IgA and IgM titers were restricted to patients who had suffered from myocardial infarction earlier in their lives. In conclusion, we show that PTCA induces a stimulation of the humoral immune response against C. pneumoniae. These data support the idea that plaque disruption during angioplasty might make hidden chlamydial antigens accessible to the immune system.

To study the effect of transcutaneous electrical nerve stimulation (TENS) on coronary vasomotion, patients with New York Heart Association class III angina pectoris and significant single-vessel left coronary artery disease and who were also scheduled for elective percutaneous transluminal coronary angioplasty, were allocated to a study group (precordial actual TENS, n = 10) and a control group (precordial simulated TENS, n = 5, and TENS on the back, n = 3). Coronary volumetric flow was assessed in the stenotic and nonstenotic coronary artery before and after neurostimulation. The diameter tin millimeters) of the stenotic coronary artery was reduced in the study group after actual TENS (from 2.73 +/- 0.55 by 0.12 +/- 0.11; p = 0.008). In the nonstenotic coronary artery, the diameter increased in the study group (from 2.64 +/- 0.43 by 0.24 +/- 0.15; p = 0.01). In both the stenotic and nonstenotic coronary arteries, no effect was shown on the average peak velocity (centimeters per second) in the study group. The coronary volumetric flow (milliliters per minute) was reduced in the stenotic artery of the study group (from 62 +/- 18 by 8 +/- 7; p = 0.007). In the nonstenotic coronary artery, volumetric flow increased in the study group (from 57 +/- 18 by 11 +/- 10; p = 0.007). In the control group, simulated TENS and TENS on the back had no effect on the diameter of the artery, average peak velocity, or volumetric flow. In addition, in all patients, TENS had no effect on the total volumetric flow of the left coronary artery and hemodynamic variables during the study period. This observation suggests that TENS modulates regional coronary vasomotion in patients with coronary artery disease. (C) 1998 by Excerpta Medico, Inc.

Autonomic neuropathy is a well-known and prognostically important feature of systemic amyloidosis. In other conditions, autonomic function is commonly assessed by cardiovascular reflex rests, described by Ewing, but the feasibility of these tests has not been investigated in patients with systemic amyloidosis. We studied autonomic function in amyloidotic patients using cardiovascular tests and assessed their feasibility. Patients with AA, AL and ATTR amyloidosis participated. In all patients, cardiovascular reflex testing (mental arithmetic stress test and head-lip tilting, besides the Ewing-tests) was performed. Of the 46 patients included, only 28 patients could perform all 4 Ewing-tests. In particular, patients with AA amyloidosis secondary to rheumatoid arthritis could not perform standing up and the isometric handgrip test, However, when the mental stress test replaced the handgrip test and head-up tilting replaced standing up, in 45 of the 46 patients, autonomic function could be assessed with cardiovascular reflex tests. Half of the patients with AA amyloidosis had signs of autonomic neuropathy-which was more than expected. We propose to replace the isometric handgrip test with the mental arithmetic stress test and standing up with head-up tilting if a patient is not able to perform these tests.

The diagnosis of coronary vasospasm in chronic vasospastic angina is established by the history of typical nocturnal angina pectoris with rapid relief after sublingual nitroglycerin, concomitant ST-segment elevation on the electrocardiogram and a recent normal coronary angiogram, True vasospasm may subsequently be confirmed on a coronary angiogram, either spontaneously or by provokation with acethylcholine. The authors show a case of acute vasospasm induced by a cold presser test in a 40-year-old man who had onset variant angina, Transient reduction of regional myocardial perfusion, angina pectoris at rest, and ST-segment elevation solved after administration of nitroglycerin.

Extensive myocardial bridging in the left anterior descending coronary artery was found in a 46 year old survivor of sudden cardiac near-death. Positron emission tomography and dobutamine stress echocardiography revealed ischaemia in the myocardium distal to the bridging. Spasm was excluded as cause of the ischaemia by intracoronary infusion of acetylcholine. Further evaluation of the haemodynamic importance of the bridging using intracoronary Doppler flow velocity measurements revealed an abnormal flow reserve. Dobutamine stress during coronary angiography caused increased mechanical compression during diastole. This was accompanied by multiple premature ventricular contractions. After a debridging operation the flow velocity reserve was normal. The abnormalities found during dobutamine stress had disappeared. Unexpectedly, a spasm was inducible. This may have been due to local oedema or scar formation after the operation. For the evaluation of the haemodynamic importance of myocardial bridging, intracoronary Doppler flow velocity measurements and angiography during dobutamine stress may be helpful in clinical decision making.

Basophilic or mucoid degeneration of the intima in the coronary arteries is an extremely rare cause of premature atherosclerosis. An unusual case of fatal basophilic degeneration of the coronary arteries 142 days after delivery is reported. (C) 1996 Wiley-Liss, Inc.