ABSTRACT
AIMS: Remnant cholesterol (RC) is the cholesterol content within triglyceride-rich lipoproteins. It promotes atherosclerotic cardiovascular disease beyond LDL cholesterol (LDL-C). The prognostic role of RC in patients with ST-segment elevation myocardial infarction (STEMI) is unknown. We aimed to estimate RC-related risk beyond LDL-C in patients with STEMI. METHODS AND RESULTS: A total of 6602 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) from 1999 to 2016 were included. Remnant cholesterol was calculated as total cholesterol minus LDL-C minus HDL cholesterol. Adjusted Cox models were used to estimate the association between continuous RC levels and all-cause mortality, cardiovascular death, ischaemic stroke, and recurrent myocardial infarction (MI) at long-term (median follow-up of 6.0 years). Besides, discordance analyses were applied to examine the risk of the discordantly high RC (RC percentile rank minus LDL-C percentile rank > 10 units) compared with the discordantly low RC (LDL-C percentile rank minus RC percentile rank > 10 units). The concordance was defined as the percentile rank difference between RC and LDL-C ≤ 10 units. The median age of patients was 63 years [interquartile range (IQR) 54-72] and 74.8% were men. There were 2441, 1651, and 2510 patients in the discordantly low RC group, concordant group, and discordantly high RC group, respectively. All outcomes in the discordantly high RC group were higher than the other groups, and the event rate of all-cause mortality in this group was 31.87%. In the unadjusted analysis, the discordantly high RC was associated with increased all-cause mortality [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.63-2.04] and increased cardiovascular death (HR 1.79, 95% CI 1.55-2.06) compared with the discordantly low RC. In an adjusted model, RC was associated with higher all-cause mortality (HR 1.14, 95% CI 1.07-1.22). The discordantly high RC was associated with increased all-cause mortality (adjusted HR 1.55, 95% CI 1.37-1.75) and increased cardiovascular death (adjusted HR 1.47, 95% CI 1.25-1.72) compared with the discordantly low RC. There were no associations between RC and ischaemic stroke or recurrent MI. CONCLUSION: In patients with STEMI treated with primary PCI, elevated RC levels beyond LDL-C and discordantly high RC were independently associated with increased all-cause mortality.
In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), elevated remnant cholesterol (RC) levels beyond LDL cholesterol were independently associated with increased all-cause mortality.About 38% of patients with STEMI present discordantly high RC, which is associated with elevated all-cause mortality and cardiovascular death.Remnant cholesterol as a continuous variable is associated with higher all-cause mortality.
Subject(s)
Biomarkers , Cholesterol , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/diagnosis , Male , Middle Aged , Female , Aged , Cholesterol/blood , Biomarkers/blood , Risk Assessment , Risk Factors , Retrospective Studies , Triglycerides/blood , Cause of Death , Time Factors , Recurrence , Cholesterol, LDL/blood , Treatment OutcomeABSTRACT
CONTEXT: Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH). OBJECTIVE: We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH. METHODS: Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a). RESULTS: We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15â mg/dL (29â nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50â mg/dL (105â nmol/L), while 2% had levels greater than or equal to 180â mg/dL (389â nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a). CONCLUSION: Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.
Subject(s)
Hyperlipoproteinemia Type II , Lipoprotein(a) , Humans , Cholesterol, LDL , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/epidemiology , Heart Disease Risk Factors , Denmark/epidemiologyABSTRACT
Importance: Brain health is most likely compromised after hospitalization for COVID-19; however, long-term prospective investigations with matched control cohorts and face-to-face assessments are lacking. Objective: To assess whether long-term cognitive, psychiatric, or neurological complications among patients hospitalized for COVID-19 differ from those among patients hospitalized for other medical conditions of similar severity and from healthy controls. Design, Setting, and Participants: This prospective cohort study with matched controls was conducted at 2 academic hospitals in Copenhagen, Denmark. The case cohort comprised patients with COVID-19 hospitalized between March 1, 2020, and March 31, 2021. Control cohorts consisted of patients hospitalized for pneumonia, myocardial infarction, or non-COVID-19 intensive care-requiring illness between March 1, 2020, and June 30, 2021, and healthy age- and sex-matched individuals. The follow-up period was 18 months; participants were evaluated between November 1, 2021, and February 28, 2023. Exposures: Hospitalization for COVID-19. Main Outcomes and Measures: The primary outcome was overall cognition, assessed by the Screen for Cognitive Impairment in Psychiatry (SCIP) and the Montreal Cognitive Assessment (MoCA). Secondary outcomes were executive function, anxiety, depressive symptoms, and neurological deficits. Results: The study included 345 participants, including 120 patients with COVID-19 (mean [SD] age, 60.8 [14.4] years; 70 men [58.3%]), 125 hospitalized controls (mean [SD] age, 66.0 [12.0] years; 73 men [58.4%]), and 100 healthy controls (mean [SD] age, 62.9 [15.3] years; 46 men [46.0%]). Patients with COVID-19 had worse cognitive status than healthy controls (estimated mean SCIP score, 59.0 [95% CI, 56.9-61.2] vs 68.8 [95% CI, 66.2-71.5]; estimated mean MoCA score, 26.5 [95% CI, 26.0-27.0] vs 28.2 [95% CI, 27.8-28.6]), but not hospitalized controls (mean SCIP score, 61.6 [95% CI, 59.1-64.1]; mean MoCA score, 27.2 [95% CI, 26.8-27.7]). Patients with COVID-19 also performed worse than healthy controls during all other psychiatric and neurological assessments. However, except for executive dysfunction (Trail Making Test Part B; relative mean difference, 1.15 [95% CI, 1.01-1.31]), the brain health of patients with COVID-19 was not more impaired than among hospitalized control patients. These results remained consistent across various sensitivity analyses. Conclusions and Relevance: This prospective cohort study suggests that post-COVID-19 brain health was impaired but, overall, no more than the brain health of patients from 3 non-COVID-19 cohorts of comparable disease severity. Long-term associations with brain health might not be specific to COVID-19 but associated with overall illness severity and hospitalization. This information is important for putting understandable concerns about brain health after COVID-19 into perspective.
Subject(s)
COVID-19 , Myocardial Infarction , Pneumonia , Male , Humans , Middle Aged , Aged , COVID-19/complications , COVID-19/epidemiology , Prospective Studies , Critical Illness , Brain , Myocardial Infarction/complications , Myocardial Infarction/epidemiologyABSTRACT
BACKGROUND: Inflammation in ST-segment elevation myocardial infarction (STEMI) is an important contributor to both acute myocardial ischemia and reperfusion injury after primary percutaneous coronary intervention (PCI). Methylprednisolone is a glucocorticoid with potent anti-inflammatory properties with an acute effect and is used as an effective and safe treatment of a wide range of acute diseases. The trial aims to investigate the cardioprotective effects of pulse-dose methylprednisolone administered in the pre-hospital setting in patients with STEMI transferred for primary PCI. METHODS: This trial is a randomized, blinded, placebo-controlled prospective clinical phase II trial. Inclusion will continue until 378 patients with STEMI have been evaluated for the primary endpoint. Patients will be randomized 1:1 to a bolus of 250 mg methylprednisolone intravenous or matching placebo over a period of 5 min in the pre-hospital setting. All patients with STEMI transferred for primary PCI at Rigshospitalet, Copenhagen University Hospital, Denmark, will be screened for eligibility. The main eligibility criteria are age ≥ 18 years, acute onset of chest pain with < 12 h duration, STEMI on electrocardiogram, no known allergy to glucocorticoids or no previous coronary artery bypass grafting, previous acute myocardial infarction in assumed culprit, or a history with previous maniac/psychotic episodes. Primary outcome is final infarct size measured by late gadolinium enhancement on cardiac magnetic resonance (CMR) 3 months after STEMI. Secondary outcomes comprise key CMR efficacy parameters, clinical endpoints at 3 months, the peak of cardiac biomarkers, and safety. DISCUSSION: We hypothesize that pulse-dose methylprednisolone administrated in the pre-hospital setting decreases inflammation and thus reduces final infarct size in patients with STEMI treated with primary PCI. TRIAL REGISTRATION: EU-CT number: 2022-500762-10-00; Submitted May 5, 2022. CLINICALTRIALS: gov Identifier: NCT05462730; Submitted July 7, 2022, first posted July 18, 2022.
Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Adolescent , Adult , Humans , Contrast Media , Gadolinium/therapeutic use , Glucocorticoids/therapeutic use , Hospitals , Inflammation/etiology , Methylprednisolone/therapeutic use , Percutaneous Coronary Intervention/adverse effects , Prospective Studies , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Treatment OutcomeABSTRACT
BACKGROUND AND AIMS: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH. METHODS: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice. RESULTS: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant. CONCLUSIONS: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.
Subject(s)
Hyperlipoproteinemia Type II , Humans , Cholesterol, LDL/genetics , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/epidemiology , Hyperlipoproteinemia Type II/genetics , Genetic Testing , Denmark/epidemiologyABSTRACT
In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy.
Subject(s)
Heart Failure , Ischemic Postconditioning , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Heart Failure/epidemiology , Humans , Ischemic Postconditioning/adverse effects , Ischemic Postconditioning/methods , Percutaneous Coronary Intervention/methods , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/surgery , Thrombectomy/methods , Treatment OutcomeABSTRACT
BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.
Subject(s)
Acute Coronary Syndrome/diagnostic imaging , Computed Tomography Angiography , Coronary Angiography , Coronary Stenosis/diagnostic imaging , Aged , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective StudiesABSTRACT
Background: Takotsubo cardiomyopathy (TTC) is a syndrome of acute non-coronary heart failure with similar symptoms and electrocardiograms to acute anterior ST-elevation myocardial infarction (STEMI). Little is known about the pathophysiology of TTC. We assessed admission plasma concentrations of biomarkers reflecting neuroendocrine response (copeptin, mid-regional-pro-adrenomedullin, pro-atrial-natriuretic-peptide, soluble thrombomodulin (sTM), syndecan-1) and inflammation (suppression-of-tumorigenicity 2 (ST2), high-sensitive C-reactive-protein) in TTC patients and compared to patients with acute anterior STEMI.Materials and methods: Twenty TTC patients were matched with 40 STEMI patients by age, gender and left ventricular ejection fraction. Blood was sampled upon hospital admission immediately before acute coronary angiography.Results: The groups had similar comorbidities. TTC patients had higher plasma concentrations of sTM: 7.94 (5.89;9.61) vs. 6.42 (5.50;7.82)ng/ml, p = 0.04 and ST2 (53 (32;157) vs. 45 (31;55)ng/ml, p = 0.008) and higher heart rate: 101 ([Formula: see text]33) vs. 76([Formula: see text]14)bpm, p = 0.0001, but lower concentrations of copeptin (10.4 (7.6;39) vs. 92.3 (13;197)pmol/l, p < 0.05) and troponin T (348 (98;759) vs. 1190 (261;4105)ng/l, p = 0.04).Conclusion: TTC patients had higher plasma concentrations of sTM and ST2, higher heart rate and lower copeptin and troponin T concentrations compared to acute anterior STEMI patients. This study contributes to the hypothesis that TTC patients have endothelial cell damage and are hemodynamically more stable than patients with acute anterior STEMI on admission.
Subject(s)
Biomarkers/blood , ST Elevation Myocardial Infarction/diagnosis , Takotsubo Cardiomyopathy/diagnosis , Aged , Diagnosis, Differential , Endothelial Cells/pathology , Female , Glycopeptides/blood , Heart Rate , Hemodynamics , Humans , Interleukin-1 Receptor-Like 1 Protein/blood , Male , Middle Aged , ST Elevation Myocardial Infarction/blood , Takotsubo Cardiomyopathy/blood , Thrombomodulin/blood , Troponin T/bloodABSTRACT
BACKGROUND: Thirty-day mortality in ST-elevation myocardial infarction (STEMI) patients is primarily driven by cardiogenic shock (CS). High neutrophil counts and high neutrophil/lymphocyte ratios (NLR) have previously been associated with mortality in STEMI patients; however, there is only sparse knowledge regarding their association with CS. PURPOSE: We sought to assess the associations between neutrophil count and NLR with the development of CS as well as 30-day mortality in STEMI patients. METHODS: Patients admitted with STEMI at two tertiary Heart Centres throughout 1 year were included in the study and stratified into quartiles according to the level of leukocyte count upon admission. The primary endpoint was development of CS both before (early CS) and after leaving the catheterization laboratory (late CS). The secondary endpoint was all-cause 30-day mortality. RESULTS: A total of 1,892 STEMI patients were included, whereof 194 (10%) developed CS while 122 (6.4%) died within 30 days. Patients in the highest quartile of neutrophils (OR: 2.54; 95% CI: 1.40-4.60; Pâ=â0.002) and NLR (OR: 3.64; 95% CI: 2.02-6.54; P<0.0001) were at increased risk of developing late CS compared with patients in the lower quartiles, whereas there was no risk difference across quartiles regarding development of early CS. Both biomarkers correlated strongly to an increased 30-day mortality (plogrank<0.0001) and, moreover, a high level of neutrophils was independently associated with 30-day mortality (HR: 1.95; 95% CI: 1.25-3.03; Pâ=â0.003). CONCLUSION: High levels of neutrophils and a high NLR upon admission for STEMI were independently associated with an increased risk of developing late CS and, additionally, both biomarkers showed association to 30-day mortality.
Subject(s)
Leukocyte Count , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/complications , Shock, Cardiogenic/blood , Shock, Cardiogenic/etiology , Aged , Biomarkers/blood , Cohort Studies , Female , Humans , Male , Middle Aged , Patient Admission , Predictive Value of Tests , Survival RateABSTRACT
OBJECTIVES: Given the novelty of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), little is known regarding overall implementation or clinical characteristics among patients who initiate treatment. We aimed to assess the total number of patients initiated on PCSK9i along with a description of the clinical characteristics and lipid lowering treatment (LLT) of such patients. SETTING: A register-based descriptive cohort study of patients receiving a PCSK9i in the time period from 01 January 2016 to 31 March 2017 using a cross linkage between three nationwide Danish registers. Information regarding PCSK9i prescriptions, patient demographics, concurrent pharmacotherapy, comorbidities and previous coronary procedures was identified. RESULTS: Overall, 137 patients initiated treatment with PCSK9i in the study period from 11 in the first quarter of 2016 to 40 in the first quarter of 2017. The majority had a history of ischaemic heart disease (IHD) (67.9%) with ischaemic stroke and diabetes mellitus being present in 7.3% and 16.8% of patients, respectively. All patients initiated on PCSK9i had been previously prescribed statin treatment with atorvastatin and simvastatin being most frequently prescribed in 53% and 36% of patients, respectively. The majority of patients had received both statins and ezetimibe (94.9%) and approximately half of these patients had also received bile acid sequestrant (45.3%). Clinical characteristics mainly differed in patients receiving triple LLT compared with patients not receiving triple LLT in the regards of heart failure. CONCLUSION: Patients treated with PCSK9i were rare, characterised by having IHD and had received various and intensive conventional LLT prior to PCSK9i initiation in agreement with current international guidelines.
Subject(s)
Anticholesteremic Agents/therapeutic use , Hypercholesterolemia/drug therapy , Hypercholesterolemia/epidemiology , PCSK9 Inhibitors , Practice Patterns, Physicians' , Aged , Cholesterol, LDL/blood , Denmark/epidemiology , Diabetes Mellitus/epidemiology , Ezetimibe/therapeutic use , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Myocardial Ischemia/epidemiology , Stroke/epidemiologyABSTRACT
AIMS: The diagnosis of cardiogenic shock depends on clinical signs of poor perfusion and low blood pressure. Lactate concentration will increase with poor tissue perfusion, and it has prognostic value in cardiogenic shock patients. We sought to assess the prognostic value of lactate concentration in subjects admitted with suspected ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: In 2,094 (93%) out of 2,247 consecutive suspected STEMI-subjects, lactate concentration was measured on admission. The prognostic value of lactate concentration on 30-day mortality was assessed in addition to clinical signs of peripheral hypoperfusion, systolic blood pressure (sBP), and left ventricular ejection fraction (LVEF) in multivariable models.Lactate concentration added prognostic information beyond signs of peripheral hypoperfusion, sBP, and LVEF, and was independently associated with 30-day mortality (hazard ratio [95% confidence interval] 1.11 [1.07-1.14], Pâ<â0.0001). Lactate also provided predictive information on 30-day mortality to the combination of signs of peripheral hypoperfusion, sBP, and LVEF (area under the receiver-operating characteristics curve = 0.88 vs. 0.83, Pâ<â0.0001). CONCLUSIONS: In conclusion, admission lactate concentration in suspected STEMI-subjects contains prognostic information on 30-day mortality when added to variables used in cardiogenic shock-definition. We recommend lactate measurement in STEMI-subjects, especially when signs of compromised hemodynamics are present.
Subject(s)
Blood Pressure , Lactic Acid/blood , ST Elevation Myocardial Infarction , Shock, Cardiogenic , Aged , Disease-Free Survival , Female , Humans , Male , Middle Aged , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/physiopathology , Shock, Cardiogenic/blood , Shock, Cardiogenic/mortality , Shock, Cardiogenic/physiopathology , Survival Rate , Time FactorsABSTRACT
OBJECTIVES: The study sought to investigate adrenergic activity in patients with takotsubo cardiomyopathy (TTC). BACKGROUND: TTC is a specific type of reversible heart failure possibly caused by excessive catecholamine stimulation of the myocardium. Scintigraphic iodine-123-meta-iodobenzylguanidine (mIBG) imaging of the heart and measurement of plasma catecholamines can be used to assess adrenergic activity in vivo. The authors hypothesized that sympathetic nerve activity is increased in the subacute state of TTC, and this study used cardiac mIBG imaging and plasma levels of norepinephrine and epinephrine as markers to assess this hypothesis. METHODS: In this study, 32 patients with TTC and 20 controls were examined at admission and again on follow-up with echocardiography, mIBG scintigraphy, and plasma catecholamine measurements. RESULTS: Ejection fraction (EF) was initially 36 ± 9% but increased to >60% (p = 0.0004) in all patients with TTC. In the control subjects EF was initially higher (51 ± 11%; p = 0.0004) than in the patients with TTC. However, EF of the patients with TTC exceeded that of the control subjects on follow-up (56 ± 8%; p = 0.0007). The mIBG imaging showed a lower late (4-h) heart-to-mediastinum ratio (H/Mlate) (2.00 ± 0.38) and a higher washout rate (WR) (45 ± 12%) in the subacute state of TTC, both when compared with follow-up (H/Mlate: 2.42 ± 0.45; p = 0.0004; WR: 33 ± 14%; p = 0.0004) and when compared with the control group in the subacute state (H/Mlate: 2.34 ± 0.60, p = 0.035; WR: 33 ± 19%, p = 0.026). On follow-up, no differences in mIBG parameters were observed between the TTC and control groups (H/Mlate: 2.41 ± 0.51, p = 0.93; WR: 30 ± 13%, p = 0.48) group. In the TTC group, plasma epinephrine levels were elevated in the subacute state (Log2[epinephrine]: 6.13 ± 1.04 pg/ml), both when compared with follow-up (5.25 ± 0.62 pg/ml; p = 0.0004) and when compared with the control group in the subacute state (5.46 ± 0.69 pg/ml; p = 0.044), and these levels remained elevated in the TTC group on follow-up compared with the control group (4.56 ± 0.95 pg/ml; p = 0.014). No significant differences in plasma norepinephrine levels were observed. CONCLUSIONS: The present study supports a possible role of adrenergic hyperactivity in TTC.
Subject(s)
3-Iodobenzylguanidine/administration & dosage , Heart/diagnostic imaging , Radiopharmaceuticals/administration & dosage , Takotsubo Cardiomyopathy/diagnostic imaging , Aged , Biomarkers/blood , Case-Control Studies , Echocardiography , Epinephrine/blood , Female , Heart/innervation , Humans , Male , Middle Aged , Norepinephrine/blood , Predictive Value of Tests , Prospective Studies , Stroke Volume , Sympathetic Nervous System/metabolism , Sympathetic Nervous System/physiopathology , Takotsubo Cardiomyopathy/blood , Takotsubo Cardiomyopathy/physiopathology , Ventricular Function, LeftABSTRACT
AIMS: Takotsubo cardiomyopathy (TTC) is characterized by acute completely reversible regional left ventricle (LV) akinesia and decreased tracer uptake in the akinetic region on semi-quantitative perfusion imaging. The latter may be due to normoperfusion of the akinetic mid/apical area and basal hyperperfusion. Our aim was to examine abnormalities of perfusion in TTC, and we hypothesized that basal hyperperfusion is the primary perfusion abnormality in the acute state. METHOD AND RESULTS: Twenty-five patients were diagnosed with TTC due to (i) acute onset of symptoms, (ii) typical apical ballooning, (iii) absence of significant coronary disease, and (iv) complete remission on 4-month follow-up. The patients underwent coronary angiography (CAG), echocardiography, cardiac magnetic resonance imaging (CMR), and (13)NH3/(82)Rb positron emission tomography (PET) in the acute state and-except CAG-on follow-up. Patients initially had severe heart failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers. On initial perfusion PET imaging, eight patients appeared to have normal, whereas 17 patients had impaired LV perfusion. In the latter, flow in the basal region was increased in the acute state (1.5 ± 0.1 vs. 1.2 ± 0.1 mL/g/minRPP-corrected, P < 0.01), whereas midventricular (1.7 ± 0.1 vs. 1.6 ± 0.1 mL/g/minRPP-corrected, P = 0.21) and apical (1.4 ± 0.1 vs. 1.5 ± 0.1 mL/g/minRPP-corrected, P = 0.36) flow was unchanged between acute and follow-up, and within normal range. CONCLUSION: Our results suggest an abnormal LV perfusion distribution in the acute state of TTC with basal hyperperfusion and a normoperfused akinetic region. The proportion of patients without visualized perfusion abnormalities in the acute state may represent a subgroup with fast remission.
Subject(s)
Myocardial Perfusion Imaging/methods , Takotsubo Cardiomyopathy/diagnostic imaging , Takotsubo Cardiomyopathy/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Aged , Biomarkers/blood , Coronary Angiography , Echocardiography , Electrocardiography , Female , Humans , Hyperemia , Magnetic Resonance Imaging , Male , Positron-Emission Tomography , Radiopharmaceuticals , Rubidium RadioisotopesABSTRACT
In patients with heart failure (HF) due to coronary disease, a combined evaluation of perfusion and glucose metabolism by cardiac single photon emission computed tomography (SPECT)/positron emission tomography (PET) can be used to distinguish viable from non-viable myocardium, and current guidelines recommend cardiac SPECT and fluorodeoxyglucose (FDG) PET for viability assessment. Takotsubo cardiomyopathy (TTC) is a disease characterized by acute but reversible HF leaving no scarring. To explore how robust the semi-quantitative viability criteria used in cardiac SPECT and FDG PET stands their ground in a population with TTC. From 1 September 2009 to 1 October 2012, 24 patients suspected of TTC were enrolled in a multimodality cardiac imaging research project. Echocardiography, (99m)Tc SPECT, and (18)F FDG PET were performed during the acute admission and at follow-up 4 months later. Nineteen patients had a final diagnosis of TTC consistent with Mayo Clinic Diagnostic Criteria. Three of these patients were excluded from further analysis, since wall motion abnormalities were not persistent at the time of nuclear imaging. The remaining sixteen patients exhibited a distinct pattern with HF, "apical ballooning" and a perfusion-metabolism defect in the midventricular/apical region. When viability criteria were applied, they identified significant scarring/limited hibernation in the akinetic part of the left ventricle. However, full recovery was found in all TTC patients on follow-up. Using the current guideline-endorsed viability criteria for semiquantitative cardiac SPECT and FDG PET, these modalities failed to demonstrate the presence of viability in the acute state of TTC.
Subject(s)
Fluorodeoxyglucose F18 , Heart Ventricles/diagnostic imaging , Positron-Emission Tomography , Radiopharmaceuticals , Takotsubo Cardiomyopathy/diagnostic imaging , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed, Single-Photon , Aged , Coronary Angiography , Denmark , Female , Heart Ventricles/physiopathology , Humans , Male , Myocardial Contraction , Predictive Value of Tests , Prognosis , Recovery of Function , Takotsubo Cardiomyopathy/physiopathology , Time Factors , Tissue Survival , Ultrasonography , Ventricular Function, LeftABSTRACT
Percutaneous renal denervation is a new treatment option for patients with resistant hypertension and little is known about the eligibility of patients referred. 100 consecutive patients were referred for renal denervation from March 2011 through September 2012. Clinical data were prospectively extracted from letters and documents from referring clinics and from our physical examination. Of the 100 patients included, 68 were men and the mean age was 60 (± 12) years. Office blood pressure was 176 (± 28)/99 (± 19) mmHg and 24-h ambulatory blood pressure 156 (± 20)/88 (± 13) mmHg. The mean number of antihypertensive agents was 4.0 (± 1.6). Nearly four-fifths (82%) of the patients were categorized as having resistant hypertension based on the criteria stated by The American Heart Association's stated criteria. Nine patients declined interest in renal denervation before completing the clinical workup program. Thus, 91 patients were screened, and of those 51 were found to be candidates for renal denervation. Forty patients were not candidates, of which secondary hypertension was the most common cause (n = 10). Only 51% of patients referred for renal denervation were eligible for treatment. The prevalence of secondary hypertension was 10% of the referred population. Secondary hypertension should therefore be considered in the evaluation of candidates for renal denervation.
Subject(s)
Blood Pressure Monitoring, Ambulatory/statistics & numerical data , Hypertension/epidemiology , Kidney/innervation , Sympathectomy/methods , Blood Pressure Monitoring, Ambulatory/methods , Denmark/epidemiology , Female , Humans , Hypertension/drug therapy , Hypertension/etiology , Kidney/physiopathology , Male , Middle Aged , Prospective StudiesABSTRACT
Blood pressure measurement should follow recommended procedures, otherwise incorrect diagnoses will follow resulting in incorrect treatment and cardiovascular events. The standard for clinical blood pressure measurement is the auscultatory method, but mercury sphygmomanometers can still be used. Blood pressure measurement at home using 24-hour or home blood pressure has documented a better reproducibility and predicts cardiovascular event more precisely than clinic blood pressure. 24-hour measurement or home blood pressure measurement should be performed in patients with suspected hypertension without hypertensive organ damage to reveal white-coat hypertension.
Subject(s)
Blood Pressure Determination , Hypertension/diagnosis , Adult , Blood Pressure Determination/instrumentation , Blood Pressure Determination/methods , Blood Pressure Determination/standards , Blood Pressure Monitoring, Ambulatory , Child , Humans , Manometry/instrumentation , PostureABSTRACT
Isolated systolic hypertension (ISH) is a major risk factor for cardiovascular complications. Nevertheless, data on the prevalence in a representative population do not seem to be available. The prevalence of ISH and the white coat effect was thus studied in a cross-sectional survey of 2806 inhabitants aged 70-80 years. In untreated subjects, the prevalence of ISH was 17.4% (95% CI 14.9-20.2) in women and 13.5% (95% CI 11.3-15.9) in men using clinic blood pressure at first visit. The prevalence increased significantly with age. The prevalence was reduced to 10.4% when using the average of all-visits clinic blood pressures. By a simulation model, it was demonstrated that his reduction mainly resulted from a regression towards the mean. Average all-visits clinic blood pressure was 172.6 +/- 10.4/81.1 +/- 6.0 mmHg. Less than one-third of those with all-visit ISH had sustained ISH. Identifying subjects with sustained ISH requires measurements in more than three visits.
Subject(s)
Blood Pressure Monitoring, Ambulatory/statistics & numerical data , Hypertension/epidemiology , Systole , Aged , Aged, 80 and over , Circadian Rhythm , Cohort Studies , Computer Simulation , Denmark/epidemiology , Diastole , Female , Humans , Male , Models, Cardiovascular , Prevalence , Rural Population , Sampling Studies , Urban PopulationABSTRACT
Experiments 1 and 2 tested the hypothesis that cholinergic receptor antagonists impair place learning in a water maze by interfering with the processing of distal, visual cues. Extramaze cues were offered to rats in the form of geometrical patterns arranged on the inner circumference of a curtain surrounding the water maze. In Experiment 1 the animals were offered both the distal cues and proximal cues in the form of pingpong balls in fixed positions on the surface of the water while only distal cues were present in Experiment 2. Animals were injected with either scopolamine (0.5 mg/kg body wt) or saline 20 min prior to the daily place learning sessions. Upon reaching criterion level performance the animals were tested on "rotation" sessions on which the distal cues were displaced. The outcome of such "rotations" demonstrated that-regardless of the presence or absence of proximal cues-scopolamine-treated rats relied at least as much as normal animals on the distal cues. The acquisition phase of both Experiments 1 and 2 demonstrated an almost complete lack of scopolamine-associated impairment in acquisition and performance of the place learning task. In Experiment 3 (when scopolamine was no longer administered) the subjects of Experiment 2 were exposed to a series of pharmacological "challenges" of their place learning performance and eventually to surgical ablation of the anteromedial prefrontal cortex. The outcome of the pharmacological challenges and the postoperative test of task performance demonstrated that the place learning performance of animals which had acquired the task under scopolamine was mediated by a neural substrate dissimilar to the substrate of task performance in normal animals. Rats acquiring the task while deprived of the cholinergic system demonstrated above-normal contributions to task mediation from catecholaminergic-probably dopaminergic-mechanisms and tentative results pointed to a "shift" toward prefrontal task mediation.