Ulrik M. Mogensen

Clinical characteristics and major comorbidities in heart failure patients more than 85 years of age compared with younger age groups

Heart failure (HF) is increasingly prevalent among the growing number of elderly people, but not well studied. We sought to evaluate disease pattern and importance of prognostic factors among very elderly patients with HF.

Early diastolic strain rate in relation to systolic and diastolic function and prognosis in acute myocardial infarction: a two-dimensional speckle-tracking study

AIMS Diastolic dysfunction in acute myocardial infarction (MI) is associated with adverse outcome. Recently, the ratio of early mitral inflow velocity (E) to global diastolic strain rate (esr) has been proposed as a marker of elevated LV filling pressure. However, the prognostic value of this measure has not been demonstrated in a large-scale setting when existing parameters of diastolic function are known. We hypothesized that the E/esr ratio would be independently associated with an adverse outcome in patients with MI. METHODS AND RESULTS We prospectively included patients with MI and performed echocardiography with comprehensive diastolic evaluation including E/esr. The relationship between E/esr and the primary composite endpoint (all-cause mortality, hospitalization for heart failure (HF), stroke, and new onset atrial fibrillation) was analysed with Cox models. A total of 1048 patients (mean age 63 ± 12, 73% male) were included and 142 patients (13.5%) reached the primary endpoint (median follow-up 29 months). A significant prognostic value was found for E/esr [hazard ratio (HR) per 1 unit change: 2.36, 95% confidence interval (CI): 2.02-2.75, P < 0.0001]. After multivariable adjustment E/esr remained independently related to the combined endpoint (HR per 1 unit change, 1.50; CI: 1.05-2.13, P = 0.02). The prognostic value of E/esr was driven by mortality (HR per 1 unit change, 2.52; CI: 2.09-3.04, P < 0.0001) and HF admissions (HR per 1 unit change, 2.79; CI: 2.23-3.48, P < 0.0001). CONCLUSION Deformation-based E/esr contributes important information about global myocardial relaxation superior to velocity-based analysis and is independently associated with the outcome in acute MI.

The prognostic value of left atrial peak reservoir strain in acute myocardial infarction is dependent on left ventricular longitudinal function and left atrial size.

Background—Peak atrial longitudinal strain (PALS) during the reservoir phase has been proposed as a measure of left atrium function in a range of cardiac conditions, with the potential for added pathophysiological insight and prognostic value. However, no studies have assessed the interrelation of PALS and left ventricular longitudinal strain (global longitudinal strain) in large-scale populations in regard to prognosis. Methods and Results—We prospectively included 843 patients (mean age 62.1±11.8; 74% male) with acute myocardial infarction and measured global longitudinal strain, left atrium volumes, and PALS within 48 hours of admission. PALS was related to a composite outcome of death and heart failure hospitalization. Reduced PALS was associated with hypertension, diabetes mellitus, and Killip class >1 (P<0.05 for all). Reduced PALS was associated with impairment of all measures of left ventricular systolic and diastolic function, and the correlation between global longitudinal strain and PALS was highly significant (P<0.001; r=–0.71). During follow-up (median 23.0 months Q1–Q3, 16.8–26.0), a total of 76 patients (9.0%) reached the composite end point of which 47 patients died (5.6%), and 29 patients were hospitalized for heart failure (3.4%). PALS was significantly associated with outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.85–0.90; P<0.001); however, no independent effect of PALS (HR, 1.00; 95% CI, 0.94–1.05; P=0.87) was found when adjusting for global longitudinal strain (HR, 1.20; 95% CI, 1.09–1.33; P<0.001), maximum left atrium volume before mitral valve opening (HR, 1.02; 95% CI, 1.01–1.04; P=0.006), and age (HR, 1.06; 95% CI, 1.03–1.08; P<0.001). Conclusions—PALS provides a composite measure of left ventricular longitudinal systolic function and maximum left atrium volume before mitral valve opening, and as such contains no added information when these readily obtained measures are known.

Early Echocardiographic Deformation Analysis for the Prediction of Sudden Cardiac Death and Life-Threatening Arrhythmias After Myocardial Infarction

OBJECTIVES This study sought to hypothesize that global longitudinal strain (GLS) as a measure of infarct size, and mechanical dispersion (MD) as a measure of myocardial deformation heterogeneity, would be of incremental importance for the prediction of sudden cardiac death (SCD) or malignant ventricular arrhythmias (VA) after acute myocardial infarction (MI). BACKGROUND SCD after acute MI is a rare but potentially preventable late complication predominantly caused by malignant VA. Novel echocardiographic parameters such as GLS and MD have previously been shown to identify patients with chronic ischemic heart failure at increased risk for arrhythmic events. Risk prediction during admission for acute MI is important because a majority of SCD events occur in the early period after hospital discharge. METHODS We prospectively included patients with acute MI and performed echocardiography, with measurements of GLS and MD defined as the standard deviation of time to peak negative strain in all myocardial segments. The primary composite endpoint (SCD, admission with VA, or appropriate therapy from a primary prophylactic implantable cardioverter-defibrillator [ICD]) was analyzed with Cox models. RESULTS A total of 988 patients (mean age: 62.6 ± 12.1 years; 72% male) were included, of whom 34 (3.4%) experienced the primary composite outcome (median follow-up: 29.7 months). GLS (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 1.25 to 1.53; p < 0.0001) and MD (HR/10 ms: 1.38; 95% CI: 1.24 to 1.55; p < 0.0001) were significantly related to the primary endpoint. GLS (HR 1.24; 95% CI: 1.10 to 1.40; p = 0.0004) and MD (HR/10 ms: 1.15; 95% CI: 1.01 to 1.31; p = 0.0320) remained independently prognostic after multivariate adjustment. Integrated diagnostic improvement (IDI) and net reclassification index (NRI) were significant for the addition of GLS (IDI: 4.4% [p < 0.05]; NRI: 29.6% [p < 0.05]), whereas MD did not improve risk reclassification when GLS was known. CONCLUSIONS Both GLS and MD were significantly and independently related to SCD/VA in these patients with acute MI and, in particular, GLS improved risk stratification above and beyond existing risk factors.

Cardiovascular Autonomic Neuropathy and Subclinical Cardiovascular Disease in Normoalbuminuric Type 1 Diabetic Patients

Cardiovascular autonomic neuropathy (CAN) is associated with increased mortality in diabetes. Since CAN often develops in parallel with diabetic nephropathy as a confounder, we aimed to investigate the isolated impact of CAN on cardiovascular disease in normoalbuminuric patients. Fifty-six normoalbuminuric, type 1 diabetic patients were divided into 26 with (+) and 30 without (−) CAN according to tests of their autonomic nerve function. Coronary artery plaque burden and coronary artery calcium score (CACS) were evaluated using computed tomography. Left ventricular function was evaluated using echocardiography. Blood pressure and electrocardiography were recorded through 24 h to evaluate nocturnal drop in blood pressure (dipping) and pulse pressure. In patients +CAN compared with −CAN, the CACS was higher, and only patients +CAN had a CACS >400. A trend toward a higher prevalence of coronary plaques and flow-limiting stenosis in patients +CAN was nonsignificant. In patients +CAN, left ventricular function was decreased in both diastole and systole, nondipping was more prevalent, and pulse pressure was increased compared with −CAN. In multivariable analysis, CAN was independently associated with increased CACS, subclinical left ventricular dysfunction, and increased pulse pressure. In conclusion, CAN in normoalbuminuric type 1 diabetic patients is associated with distinct signs of subclinical cardiovascular disease.

Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors and glucagon‐like peptide‐1 (GLP‐1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long‐term safety compared with conventional combination therapies are limited.

Sulfonylurea in combination with insulin is associated with increased mortality compared with a combination of insulin and metformin in a retrospective Danish nationwide study

Aims/hypothesisIndividual sulfonylureas (SUs) and metformin have, in some studies, been associated with unequal hypoglycaemic, cardiovascular and mortality risks when used as monotherapy in type 2 diabetes. We investigated the outcomes in patients treated with different combinations of SUs and insulin vs a combination of metformin and insulin in a retrospective nationwide study.MethodsAll Danish individuals using dual therapy with SU + insulin or metformin + insulin without prior myocardial infarction (MI) or stroke were followed from 1 January 1997 to 31 December 2009 in nationwide registries. Risks of all-cause mortality, cardiovascular death, hypoglycaemia and a composite endpoint of MI, stroke and cardiovascular death were compared. Rate ratios (RR) [95% CIs] were calculated using time-dependent multivariable Poisson regression analysis.ResultsA total of 11,081 patients used SU + insulin and 16,910 used metformin + insulin. Patients receiving metformin + insulin were younger and had less comorbidity and a longer history of glucose-lowering treatment. SU + insulin was associated with higher mortality rates compared with metformin + insulin (76–126 vs 23 per 1,000 person-years). In adjusted analyses, SU + insulin was associated with increased all-cause mortality (RR 1.81 [1.63, 2.01]), cardiovascular death (RR 1.35 [1.14, 1.60]) and the composite endpoint (RR 1.25 [1.09, 1.42]) compared with metformin + insulin. Hypoglycaemia was more frequent with SU + insulin than with metformin + insulin (17–23 vs six events per 1,000 person-years) and was associated with increased mortality (RR 2.13 [1.97, 2.37]). There were no significant differences in risk between individual SUs in combination with insulin.Conclusions/interpretationIn combination with insulin, the use of SUs was associated with increased mortality compared with metformin. There were no significant risk differences between SUs.

Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients With Heart Failure and Preserved Ejection Fraction: A Report From the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction).

Background: In patients with heart failure and preserved ejection fraction, little is known about the characteristics of, and outcomes in, those with and without diabetes mellitus. Methods: We examined clinical and echocardiographic characteristics and outcomes in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Ejection Fraction) according to history of diabetes mellitus. Cox regression models were used to estimate hazard ratios for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. Results: Overall, 1134 of 4128 patients (27%) had diabetes mellitus. Compared with those without diabetes mellitus, they were more likely to have a history of myocardial infarction (28% versus 22%), higher body mass index (31 versus 29 kg/m2), worse Minnesota Living With Heart Failure score (48 versus 40), higher median N-terminal pro-B-type natriuretic peptide concentration (403 versus 320 pg/mL; all P<0.01), more signs of congestion, but no significant difference in left ventricular ejection fraction. Patients with diabetes mellitus had a greater left ventricular mass and left atrial area than patients without diabetes mellitus. Doppler E-wave velocity (86 versus 76 cm/s; P<0.0001) and the E/e’ ratio (11.7 versus 10.4; P=0.010) were higher in patients with diabetes mellitus. Over a median follow-up of 4.1 years, cardiovascular death or heart failure hospitalization occurred in 34% of patients with diabetes mellitus versus 22% of those without diabetes mellitus (adjusted hazard ratio, 1.75; 95% confidence interval, 1.49–2.05), and 28% versus 19% of patients with and without diabetes mellitus died (adjusted hazard ratio, 1.59; confidence interval, 1.33–1.91). Conclusions: In heart failure with preserved ejection fraction, patients with diabetes mellitus have more signs of congestion, worse quality of life, higher N-terminal pro-B-type natriuretic peptide levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes mellitus on outcomes in heart failure with preserved ejection fraction and whether they are modifiable. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.

All-cause mortality and cardiovascular effects associated with the DPP-IV inhibitor sitagliptin compared with metformin, a retrospective cohort study on the Danish population

We performed a retrospective cohort study, investigating the clinical outcomes including mortality and cardiovascular disease of sitagliptin compared with metformin monotherapies.

Global left ventricular longitudinal strain is closely associated with increased neurohormonal activation after acute myocardial infarction in patients with both reduced and preserved ejection fraction: a two‐dimensional speckle tracking study

N‐terminal pro brain natriuretic peptide (NT‐proBNP) is released in response to increased myocardial wall stress and is associated with adverse outcome in acute myocardial infarction. However, little is known about the relationship between longitudinal deformation indices and NT‐proBNP.