| 1. |
- Larsen, Anders Hostrup, et al.
(author)
-
A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes
- 2020
-
In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:9, s. 1628-1637
-
Journal article (peer-reviewed)abstract
- AimsThe present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes. Methods and resultsThirty-six HFrEF patients (ejection fraction 378%; median age 66years) were randomised to metformin (n = 19) or placebo (n = 17) for 3months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by C-11-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 +/- 550 mg/day) increased WMI [absolute mean difference, 1.0mmHg.mL.m(-2).10(6); 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6mL O-2.100 g(-1).min(-1); P = 0.014). Cardiac stroke work was preserved (-2J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups. ConclusionMetformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.
|
|
| 2. |
- Clemmensen, Tor Skibsted, et al.
(author)
-
Left Ventricular Pressure-Strain-Derived Myocardial Work at Rest and during Exercise in Patients with Cardiac Amyloidosis
- 2020
-
In: Journal of the American Society of Echocardiography. - : MOSBY-ELSEVIER. - 0894-7317 .- 1097-6795. ; 33:5, s. 573-582
-
Journal article (peer-reviewed)abstract
- Background: Left ventricular pressure-strain-derived myocardial work index (LVMWI) is a novel, noninvasive method for left ventricular (LV) function evaluation in relation to LV pressure dynamics. LV global longitudinal strain (LVGLS) has proven benefit for diagnosis and risk stratification in patients with cardiac amyloidosis (CA), but LVGLS does not adjust for loading conditions. The aim of the present study was to characterize LVMWI at rest and during exercise in patients with CA. Methods: A total of 155 subjects were retrospectively included. These subjects comprised 100 patients with CA and 55 healthy control subjects. All patients had previously undergone comprehensive two-dimensional echocardiographic examinations at rest. Furthermore, a subgroup 27 patients with CA and 41 control subjects was examined using sennisu pine exercise stress echocardiography. Results: Patients with CA had significantly lower LVGLS, LVMWI, and LV myocardial work efficiency (LVMWE) than control subjects (P < .0001 for all). The reduction in LV myocardial performance was more pronounced in the basal segments, which led to significant alterations in the average apical-to-basal segmental ratios between patients with CA and control subjects (LVGLS, 2.6 [1.9 to 4.1] vs 1.3 [1.2 to 1.5]; LVMWI, 2.6 [1.7 to 3.8] vs 1.3 [1.1 to 1.5]; LVMWE, 1.1 [1.0 to 1.3] vs 1.0 [1.0 to 1.1]; P < .0001 for all). The average increase in LVMWI from rest to peak exercise was 1,974 mm Hg% (95% CI, 1,699 to 2,250 mm Hg%; P < .0001) in control subjects and 496 mm Hg% (95% CI, 156 to 835 mm Hg%; P < .01) in patients with CA. The absolute numeric LVGLS increase was 5.6% (95% CI, 3.9% to 7.3%; P < .0001) in control subjects and only 1.2% (95% CI, -0.9% to 3.3%; P = .26) in patients with CA (between groups, P < .0001) from rest to peak exercise. The LVMWI increase in patients with CA was mediated by improvement in the apical segments (P < .0001), whereas there was no significant LVMWI alterations in the midventricular or basal segments. LVMWE remained stable during exercise in control subjects (Delta -0.6%; 95% CI, -2.5% to 1.2%; P = .50) but decreased significantly in patients with CA (Delta -2.5%; 95% CI, -4.8% to -0.2%; P < .05). Conclusions: Patients with CA have significantly reduced magnitude of LVMWI compared with healthy control subjects. With exercise, the differences are even more pronounced. Even though LVMWI increased with exercise, LVMWE decreased, suggesting inefficient myocardial energy exploitation in patients with CA.
|
|
| 3. |
- Harms, Hendrik J., et al.
(author)
-
Association of right ventricular myocardial blood flow with pulmonary pressures and outcome in cardiac amyloidosis
- 2023
-
In: JACC Cardiovascular Imaging. - : Elsevier. - 1936-878X .- 1876-7591.
-
Journal article (peer-reviewed)abstract
- Background: Cardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied.Objectives: This study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA.Methods: Cardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11C-acetate, 15O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA.Results: MBF of the right ventricle (MBFRV) and the ratio of MBFRV and MBF of the left ventricle (MBFRV/LV) for the 2 tracers were significantly correlated (r > 0.92). MBFRV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBFLV was inversely correlated with wall thickness (P < 0.0001). MBFRV/LV was significantly associated with N-terminal pro–B-type natriuretic peptide levels, New York Heart Association functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBFRV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with hazard ratio 9.0 (95% CI: 4.2-14.5), P < 0.0001).Conclusions: Measurements of MBFRV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis.
|
|
| 4. |
- Rosengren, Sara, et al.
(author)
-
Diagnostic Accuracy of [11C]PIB Positron Emission Tomography for Detection of Cardiac Amyloidosis
- 2020
-
In: JACC Cardiovascular Imaging. - : Elsevier BV. - 1936-878X .- 1876-7591. ; 13:6, s. 1337-1347
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: This dual-site study evaluated the diagnostic accuracy of the method.BACKGROUND: Pittsburgh compound ([11C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA).METHODS: The study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively.RESULTS: The diagnostic accuracy of visual inspection of [11C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [11C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [11C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [11C]PIB PET positive.CONCLUSIONS: In a dual-center setting, [11C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were [11C]PIB PET positive, indicating that the method may detect early stages of CA.
|
|
| 5. |
- Rosengren, Sara, et al.
(author)
-
Outcome prediction by myocardial external efficiency from 11C-acetate positron emission tomography in cardiac amyloidosis
- 2024
-
In: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 11:1, s. 44-53
-
Journal article (peer-reviewed)abstract
- AimsThis study aimed to study the prognostic value of myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) from 11C-acetate positron emission tomography (PET) in cardiac amyloidosis (CA) patients.Methods and resultsForty-eight CA patients, both transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, and 20 controls were included. All subjects were examined with 11C-acetate PET and echocardiography. MVO2, forward stroke volume (FSV), and left ventricular mass (LVM) were derived from 11C-acetate PET and used to calculate MEE. CA patients were followed for survival and the prognostic impact of clinical, echocardiographic, and 11C-acetate PET parameters was analysed. MVO2 and MEE were reduced in CA compared with controls, but without significant difference between deceased and surviving CA patients. The ratio of 11C-acetate PET-derived FSV and LVM was also reduced in CA and significantly lowered in deceased patients compared with survivors. In univariate analysis, New York Heart Association class, N-terminal pro-brain natriuretic peptide, and the 11C-acetate PET parameters FSV/LVM and MEE were the strongest prognostic factors. Of the 11C-acetate PET parameters, FSV/LVM was the strongest survival predictor with hazard ratio of 0.56 per 0.1 mL/g (95% confidence interval 0.39–0.81, P = 0.002) and independently prognostic in a multivariate model. MEE significantly separated deceased from surviving CA patients with the cut-off of 15.7% (P = 0.032). Survival was significantly shorter with FSV/LVM below 0.27 mL/g (P < 0.001), also when separating AL- and ATTR-CA.ConclusionsReduced MEE was associated with shorter survival in CA patients, but FSV/LVM was the strongest survival predictor and the only independently prognostic 11C-acetate PET parameter in multivariate analysis.
|
|
| 6. |
- Skibsted Clemmensen, Tor, et al.
(author)
-
Prognostic implications of left ventricular myocardial work indices in cardiac amyloidosis
- 2021
-
In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press. - 2047-2404 .- 2047-2412. ; 22:6, s. 695-704
-
Journal article (peer-reviewed)abstract
- AIMS: Left ventricular (LV) myocardial work index (LVMWI) derived from pressure-strain analysis resembles a novel non-invasive method for LV function evaluation. LV global longitudinal strain (LVGLS) has proven beneficial for risk stratification in cardiac amyloidosis (CA) patients. This study aimed to evaluate the potential additive value of LVMWI for outcome prediction in CA patients.METHODS AND RESULTS: We enrolled 100 CA patients in the period 2014-19 from Aarhus University Hospital, Denmark and Uppsala University Hospital, Sweden. All patients underwent comprehensive echocardiographic evaluation and were prospectively followed until censuring date on 31 March 2019 or death. During follow-up, we registered major adverse cardiac events (MACE) comprising heart failure requiring hospitalization and all-cause mortality. The median follow-up was 490 (228-895) days. During follow-up, a total of 42% of patients experienced MACE and 29% died. Patients with LVMWI <1043 mmHg% had higher MACE risk than patients with LVMWI >1043 mmHg% [hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.3; P = 0.01]. Furthermore, patients with LVMWI <1039 mmHg% also had higher all-cause mortality risk than patients with LVMWI >1039 mmHg% (HR 2.6, 95% CI 1.2-5.5; P < 0.05). Moreover, the apical-to-basal segmental work ratio was a significant MACE and all-cause mortality predictor. By combining LVMWI and apical-to-basal segmental work ratio, we obtained an independent model for all-cause mortality prediction (high vs. low risk: HR 6.4, 95% CI 2.4-17.1; P < 0.0001). In contrast, LVGLS did not predict all-cause mortality.CONCLUSION: LV myocardial work may be of prognostic value in CA patients by predicting both MACE and all-cause mortality.
|
|
| 7. |
- Wierup, Per, et al.
(author)
-
Moderate mitral regurgitation in patients undergoing CABG--the MoMIC trial.
- 2009
-
In: Scandinavian cardiovascular journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 43:1, s. 50-6
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The presence of mild to moderate ischemic mitral regurgitation (IMR) marks a significantly reduced long-term survival and increased hospitalizations due to heart-failure. However, it is common practice in many institutions to refrain from repairing the mitral valve in these patients. There are no available conclusive data to support this practice, and thus there is a need for an adequately powered randomized trial. STUDY DESIGN: The Moderate Mitral Regurgitation In Patients Undergoing CABG (MoMIC) trial is the first international multi-center, large-scale study to clarify whether moderate IMR in CABG patients should be corrected. A total of 550 CABG patients with moderate IMR are to be randomized to treatment of either CABG alone or CABG plus mitral valve correction. The primary end point is a composite end point of mortality and rehospitalization for heart failure at five years. The inclusion and randomization of patients started in February 2008. IMPLICATION: If correction of moderate IMR in CABG patients proves to be the superior strategy, most patients should be treated accordingly.
|
|
| 8. |
- Wierup, Per, et al.
(author)
-
The prevalence of moderate mitral regurgitation in patients undergoing CABG.
- 2009
-
In: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 43:1, s. 46-9
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to determine the prevalence of moderate ischemic mitral regurgitation (IMR) in the contemporary CABG population. We also aimed to correlate the effective regurgitant orifice area (ERO) of any regurgitant mitral valve in patients with coronary artery disease with the semiquantitative integrated scale of IMR. DESIGN: From March 15 through June 15, 2006, 510 consecutive CABG patients in three tertiary centres were included in the study. All patients showing any sign of mitral regurgitation (MR) at the referring hospital underwent a preoperative transthoracic echocardiographic estimation of the degree of MR using the integrated scale (1-4) and ERO. RESULTS: IMR was found in 141 patients (28%). The prevalence of moderate 2+ or worse IMR was 4% (95% CI; 2.5-6.1%) and the ERO corresponding to 2+ IMR or more ranged from 5 to 30 mm(2). Fourteen patients had an ERO between 15-30 mm(2). CONCLUSIONS: According to our study, patients with moderate IMR, defined as an ERO between 15-30 mm(2), account for only 2.7% (95% CI; 1.5-4.7%) of a non-emergency CABG population.
|
|
