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Background This post-hoc study investigated whether biomarkers reflecting extracellular matrix (ECM) turnover predicted cardiovascular disease (CVD), mortality, and progression of diabetic kidney disease (DKD) in individuals with type 2 diabetes (T2D) and microalbuminuria. Methods Serum levels of specific ECM turnover biomarkers were assessed in 192 participants with T2D and microalbuminuria from an observational study conducted at Steno Diabetes Center Copenhagen from 2007 to 2008. Endpoints included CVD events, mortality, and DKD progression, defined as decline in estimated glomerular filtration rate (eGFR) of >30 %. Results Participants had a mean age of 59 years, with 75 % males. Over a median follow-up of 4.9 to 6.3 years, the study recorded 38 CVD events, 24 deaths, and 40 DKD events. Elevated levels of a degradation fragment of collagen type I (C1M) were associated with an increased risk of >30 % eGFR decline, although this association was not independent of other risk factors. No significant associations were found between other ECM turnover biomarkers and DKD progression, mortality, or CVD risk. Conclusion Elevated C1M levels were linked to DKD progression in individuals with T2D and microalbuminuria, but not independently of other risk factors. None of the ECM turnover biomarkers were associated with CVD or mortality., Background: This post-hoc study investigated whether biomarkers reflecting extracellular matrix (ECM) turnover predicted cardiovascular disease (CVD), mortality, and progression of diabetic kidney disease (DKD) in individuals with type 2 diabetes (T2D) and microalbuminuria. Methods: Serum levels of specific ECM turnover biomarkers were assessed in 192 participants with T2D and microalbuminuria from an observational study conducted at Steno Diabetes Center Copenhagen from 2007 to 2008. Endpoints included CVD events, mortality, and DKD progression, defined as decline in estimated glomerular filtration rate (eGFR) of >30 %. Results: Participants had a mean age of 59 years, with 75 % males. Over a median follow-up of 4.9 to 6.3 years, the study recorded 38 CVD events, 24 deaths, and 40 DKD events. Elevated levels of a degradation fragment of collagen type I (C1M) were associated with an increased risk of >30 % eGFR decline, although this association was not independent of other risk factors. No significant associations were found between other ECM turnover biomarkers and DKD progression, mortality, or CVD risk. Conclusion: Elevated C1M levels were linked to DKD progression in individuals with T2D and microalbuminuria, but not independently of other risk factors. None of the ECM turnover biomarkers were associated with CVD or mortality.

Background: SARS-CoV-2 may trigger both vasculitis and arrhythmias as part of a multisystem inflammatory syndrome described in children as well as in adults following COVID-19 infection with only minor respiratory symptoms. The syndrome denotes a severe dysfunction of one or more extra-pulmonary organ systems, with symptom onset approximately 2–5 weeks after the COVID-19 infection. In the present case, a seemingly intractable ventricular tachycardia preceded by SARS-CoV2 infection was only managed following the diagnosis and management of aortitis. Case presentation: A 69-year-old woman was hospitalized due to syncope, following a mild COVID-19 infection. She presented with paroxysmal atrial fibrillation and intermittent ventricular tachycardia interpreted as a septum-triggered bundle branch reentry ventricular tachycardia, unaffected by amiodaron, lidocaine and adenosine. A CT-scan revealed inflammation of the aortic arch, extending into the aortic root. In the following days, the tachycardia progressed to ventricular storm with intermittent third-degree AV block. A temporary pacemaker was implanted, and radiofrequency ablation was performed to both sides of the ventricular septum after which the ventricular tachycardia was non-inducible. Following supplemental prednisolone treatment, cardiac symptoms and arrythmia subsided, but recurred after tapering. Long-term prednisolone treatment was therefore initiated with no relapse in the following 14 months. Conclusion: We present a rare case of aortitis complicated with life-threatening ventricular tachycardia presided by Covid-19 infection without major respiratory symptoms. Given a known normal AV conduction prior to the COVID-19 infection, it seems likely that the ensuing aortitis in turn affected the septal myocardium, enabling the reentry tachycardia. Generally, bundle branch reentry tachycardia is best treated with radiofrequency ablation, but if it is due to aortitis with myocardial affection, long-term anti-i

Background Diabetic kidney disease is a major cause of morbidity and mortality. Dysregulated turnover of collagen type III is associated with development of kidney fibrosis. We investigated whether a degradation product of collagen type III (C3M) was a risk marker for progression of chronic kidney disease (CKD), occurrence of cardiovascular disease (CVD), and mortality during follow up in people with type 2 diabetes (T2D) and microalbuminuria. Moreover, we investigated whether C3M was correlated with markers of inflammation and endothelial dysfunction at baseline. Methods C3M was measured in serum (sC3M) and urine (uC3M) in 200 participants with T2D and microalbuminuria included in an observational, prospective study at Steno Diabetes Center Copenhagen in Denmark from 2007-2008. Baseline measurements included 12 markers of sssinflammation and endothelial dysfunction. The endpoints were CVD, mortality, and CKD progression (>30% decline in eGFR). Results Mean (SD) age was 59 (9) years, eGFR 90 (17) ml/min/1.73m2 and median (IQR) urine albumin excretion rate 102 (39-229) mg/24-h. At baseline all markers for inflammation were positively correlated with sC3M (p≤0.034). Some, but not all, markers for endothelial dysfunction were correlated with C3M. Median follow-up ranged from 4.9 to 6.3 years. Higher sC3M was associated with CKD progression (with mortality as competing risk) with a hazard ratio (per doubling) of 2.98 (95% CI: 1.41-6.26; p = 0.004) adjusted for traditional risk factors. uC3M was not associated with CKD progression. Neither sC3M or uC3M were associated with risk of CVD or mortality. Conclusions Higher sC3M was a risk factor for chronic kidney disease progression and was correlated with markers of inflammation.

Aims Current treatment guidelines recommend implantable cardioverter-defibrillators (ICDs) in eligible patients with an estimated survival beyond 1 year. There is still an unmet need to identify patients who are unlikely to benefit from an ICD. We determined cause-specific 1-year mortality after ICD implantation and identified associated risk factors.Methods and results Using Danish nationwide registries (2000-2017), we identified 14 516 patients undergoing first-time ICD implantation for primary or secondary prevention. Risk factors associated with 1-year mortality were evaluated using multivariable logistic regression. The median age was 66 years, 81.3% were male, and 50.3% received an ICD for secondary prevention. The 1-year mortality rate was 4.8% (694/14 516). ICD recipients who died within 1 year were older and more comorbid compared to those who survived (72 vs. 66 years, P < 0.001). Risk factors associated with increased 1-year mortality included dialysis [odds ratio (OR): 3.26, confidence interval (CI): 2.37-4.49], chronic renal disease (OR: 2.14, CI: 1.66-2.76), cancer (OR: 1.51, CI: 1.15-1.99), age 70-79 years (OR: 1.65, CI: 1.36-2.01), and age >= 80 years (OR: 2.84, CI: 2.15-3.77). The 1-year mortality rates for the specific risk factors were: dialysis (13.8%), chronic renal disease (13.1%), cancer (8.5%), age 70-79 years (6.9%), and age >= 80 years (11.0%). Overall, the most common causes of mortality were related to cardiovascular diseases (62.5%), cancer (10.1%), and endocrine disorders (5.0%). However, the most common cause of death among patients with cancer was cancer-related (45.7%).Conclusion Among ICD recipients, mortality rates were low and could be indicative of relevant patient selection. Important risk factors of increased 1-year mortality included dialysis, chronic renal disease, cancer, and advanced age.

BACKGROUND: Electrical storm and incessant ventricular tachycardia (VT) are characterized by the clustering of episodes of VT or ventricular fibrillation (VF) and are associated with a poor prognosis. Autonomic nervous system activity influences VT threshold, and deep sedation may be useful for the treatment of VT emergencies.METHODS: We reviewed data from conscious patients admitted to our intensive care unit (ICU) due to monomorphic VT, polymorphic VT or VF at our tertiary center between 2010 and 2018.RESULTS: A total of 46 conscious patients with recurrent ventricular arrhythmia, refractory to initial treatment, were referred to the ICU. The majority (n = 31) were stabilized on usual care. The remaining treatment-refractory 15 patients (57 years (range 9-74), 80% males, seven with implantable cardioverter-defibrillators) with VT/VF storm (n = 11) or incessant VT (n = 4) due to ischemic heart disease (n = 10), cardiomyopathy (n = 2), primary arrhythmia (n = 2) and one patient post valve surgery, were deeply sedated and intubated. A complete resolution of VT/VF within minutes to hours was achieved in 12 patients (80%), partial resolution in two (13%) and one (7%) patient died due to ventricular free-wall rupture. One patient with recurrent VT episodes needing repeated deep sedation developed necrotic caecum. No other major complications were seen. Thirteen (87%) patients were alive after a mean follow-up of 3.7 years.CONCLUSION: Deep sedation was effective and safe for the temporary management of malignant VT/VF refractory to usual treatment. In emergencies, deep sedation may be widely accessible at both secondary and tertiary centers and a clinically useful bridge to definitive treatment of VT.

OBJECTIVE Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI formation, is prognostic for adverse outcomes in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS In a prospective, observational study, we measured PRO-C6 in the serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2 diabetes and microalbuminuria without symptoms of coronary artery disease. Patients were followed for a median of 6.5 years, and end points were a composite of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of estimated glomerular filtration rate (eGFR) of >30% (disease progression [n = 42]). Cox models were unadjusted and adjusted for the conventional risk factors of sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA 1c , plasma creatinine, and urinary albumin excretion rate. RESULTS Doubling of S-PRO-C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31–7.14]), all-cause mortality (6.91 [2.96–16.11]), and disease progression (4.81 [1.92–12.01]). Addition of S-PRO-C6 to a model containing conventional risk factors improved relative integrated discrimination by 22.5% for cardiovascular events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for disease progression (P = 0.004). U-PRO-C6 was not significantly associated with any of the outcomes. CONCLUSIONS S-PRO-C6 generated during COL VI formation predicts cardiovascular events, all-cause mortality, and disease progression in patients with type 2 diabetes and microalbuminuria.

Background We evaluated the association of cardiac adipose tissue including epicardial adipose tissue and pericardial adipose tissue with incident cardiovascular disease and mortality, coronary artery calcium, carotid intima media thickness and inflammatory markers. Design A prospective study of 200 patients with type 2 diabetes and elevated urinary albumin excretion rate (UAER). Methods Cardiac adipose tissue was measured from baseline echocardiography. The composite endpoint comprised incident cardiovascular disease and all-cause mortality. Coronary artery calcium, carotid intima media thickness and inflammatory markers were measured at baseline. Cardiac adipose tissue was investigated as continuous and binary variable. Analyses were performed unadjusted (model 1), and adjusted for age, sex (model 2), body mass index, low-density lipoprotein cholesterol, smoking, glycated haemoglobin, and systolic blood pressure (model 3). Results Patients were followed-up after 6.1 years for non-fatal cardiovascular disease (n = 29) or mortality (n = 23). Cardiac adipose tissue (p = 0.049) and epicardial adipose tissue (p = 0.029) were associated with cardiovascular disease and mortality in model 1. When split by the median, patients with high cardiac adipose tissue had a higher risk of cardiovascular disease and mortality than patients with low cardiac adipose tissue in unadjusted (hazard ratio 1.9, confidence interval: 1.1; 3.4, p = 0.027) and adjusted (hazard ratio 2.0, confidence interval: 1.1; 3.7, p = 0.017) models. Cardiac adipose tissue (p = 0.033) was associated with baseline coronary artery calcium (model 1) and interleukin-8 (models 1-3, all p < 0.039). Conclusions In type 2 diabetes patients without coronary artery disease, high cardiac adipose tissue levels were associated with increased risk of incident cardiovascular disease or all-cause mortality even after accounting for traditional cardiovascular disease risk factors. High cardiac adipose tissue amounts we

BACKGROUND: To evaluate symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) as risk markers of cardiovascular disease, all-cause mortality and deterioration in renal function in a well characterised type 2 diabetic population with microalbuminuria and without symptoms of coronary artery disease.METHODS: 200 participants followed for 6.1 years. SDMA and ADMA were measured at baseline. Endpoints included (1) composite cardiovascular endpoint (n = 40); (2) all-cause mortality (n = 26); and (3) decline in eGFR of >30% (n = 42). Cox models were unadjusted and adjusted for traditional risk factors (sex, age, systolic blood pressure, LDL-cholesterol, smoking, HbA1c, creatinine and urinary albumin excretion rate). To assess if SDMA or ADMA improved risk prediction beyond traditional risk factors we calculated c statistics and relative integrated discrimination improvement (rIDI). C statistic (area under the curve) quantifies the model's improved ability to discriminate events from non-events. rIDI quantifies the increase in separation of events and non-events on a relative scale.RESULTS: Higher SDMA was associated with increased risk of all three endpoints (unadjusted: p ≤ 0.001; adjusted: p ≤ 0.02). Higher ADMA was associated with all-cause mortality (unadjusted: p = 0.002; adjusted: p = 0.006), but not cardiovascular disease or decline in eGFR (p ≥ 0.29).The c statistic was not significant for any of the endpoints for either SDMA or ADMA (p ≥ 0.10). The rIDI for SDMA was 15.0% (p = 0.081) for the cardiovascular endpoint, 52.5% (p = 0.025) for all-cause mortality and 48.8% (p = 0.007) for decline in eGFR; for ADMA the rIDI was 49.1% (p = 0.017) for all-cause mortality.CONCLUSION: In persons with type 2 diabetes and microalbuminuria higher SDMA was associated with incident cardiovascular disease, all-cause mortality and deterioration in renal function. Higher ADMA was associated with all-cause mortality. SDMA and ADMA signific

Inappropriate implantable cardioverter-defibrillator (ICD) shock therapy is painful, stressful, and typically occurs unexpected in conscious patients and may be related to a less favourable prognosis. In our institution, we have observed four cases of multiple inappropriate ICD shocks during reset to VVI backup mode. All four patients were implanted with a St Jude Medical ICD since 2010. The reset to VVI backup mode happens as a 'safety' response when the ICD encounters errors in the software or hardware often due to electromagnetic interference. The ICD then operates in a simple mode, with only a ventricular fibrillation (VF) zone starting at 146 b.p.m., with shock therapy only and changes in sensitivity settings making the ICD more sensitive. In all cases, the reason for the multiple inappropriate shocks was that the VF zone was reached due to exercise-induced sinus tachycardia or due to oversensing during sinus rhythm. The VVI backup mode has to balance between protection from failure of ICD therapy during life-threatening ventricular arrhythmias and from inappropriate shocks. It seems the non-programmable parameters in VVI backup mode of St Jude Medical ICDs carry an unacceptable high risk of inappropriate shocks during normal rhythm as illustrated by our four cases. A higher VF zone comparable with the zones chosen by the other manufacturer would give a better balance, since it is very unlikely that a patient will need shock therapy urgently for slow ventricular tachycardia.

BACKGROUND: The optimal pacing rate during cardiac resynchronization therapy (CRT) is unknown. Therefore, we investigated the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL).METHODS: Twelve CRT patients with non-ischemic heart failure (NYHA class II-III) were enrolled in a randomized, double-blind, crossover trial, in which the basal pacing rate was set at DDD-60 and DDD-80 for 3 months (DDD-R for 2 patients). At baseline, 3 months and 6 months, we assessed sympathetic nerve activity by microneurography (MSNA), peak oxygen consumption (pVO2), N-terminal pro-brain natriuretic peptide (p-NT-proBNP), echocardiography and QoL.RESULTS: DDD-80 pacing for 3 months increased the mean heart rate from 77.3 to 86.1 (p = 0.001) and reduced sympathetic activity compared to DDD-60 (51±14 bursts/100 cardiac cycles vs. 64±14 bursts/100 cardiac cycles, p<0.05). The mean pVO2 increased non-significantly from 15.6±6 mL/min/kg during DDD-60 to 16.7±6 mL/min/kg during DDD-80, and p-NT-proBNP remained unchanged. The QoL score indicated that DDD-60 was better tolerated.CONCLUSION: In CRT patients with non-ischemic heart failure, 3 months of DDD-80 pacing decreased sympathetic outflow (burst incidence only) compared to DDD-60 pacing. However, Qol scores were better during the lower pacing rate. Further and larger scale investigations are indicated.TRIAL REGISTRATION: ClinicalTrials.gov NCT02258061.

Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P-NT-proBNP and the putative residual abnormalities in such patients are not well described. This study examined echocardiographic measurements of LV hypertrophy, atrial dilatation and LV dysfunction and their relation to P-NT-proBNP levels or subclinical coronary artery disease (CAD) in type 2 diabetic patients with microalbuminuria receiving intensive multifactorial treatment.