Johan Holm

Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries

Objective. Haemostatic imbalance may be an aetiological factor in the development of acute coronary syndromes. Inherited resistance to activated protein C (APC) is a common disorder associated with hypercoagulability and lifelong risk of venous thrombosis. APC resistance is due to a single mutation in the gene coding for coagulation factor V (FV:Q506). To test the importance of the FV:Q506 mutation in premature myocardial infarction (MI), its prevalence was investigated in Swedish patients with MI before the age of 50 years.

Manual correction of semi-automatic three-dimensional echocardiography is needed for right ventricular assessment in adults; validation with cardiac magnetic resonance

BackgroundThree-dimensional echocardiography (3DE) and semi-automatic right ventricular delineation has been proposed as an appropriate method for right ventricle (RV) evaluation. We aimed to examine how manual correction of semi-automatic delineation influences the accuracy of 3DE for RV volumes and function in a clinical adult setting using cardiac magnetic resonance (CMR) as the reference method. We also examined the feasibility of RV visualization with 3DE.Methods62 non-selected patients were examined with 3DE (Sonos 7500 and iE33) and with CMR (1.5T). Endocardial RV contours of 3DE-images were semi-automatically assessed and manually corrected in all patients. End-diastolic (EDV), end-systolic (ESV) volumes, stroke volume (SV) and ejection fraction (EF) were computed.Results53 patients (85%) had 3DE-images feasible for examination. Correlation coefficients and Bland Altman biases between 3DE with manual correction and CMR were r = 0.78, -22 ± 27 mL for EDV, r = 0.83, -7 ± 16 mL for ESV, r = 0.60, -12 ± 18 mL for SV and r = 0.60, -2 ± 8% for EF (p < 0.001 for all r-values). Without manual correction r-values were 0.77, 0.77, 0.70 and 0.49 for EDV, ESV, SV and EF, respectively (p < 0.001 for all r-values) and biases were larger for EDV, SV and EF (-32 ± 26 mL, -21 ± 15 mL and - 6 ± 9%, p ≤ 0.01 for all) compared to manual correction.ConclusionManual correction of the 3DE semi-automatic RV delineation decreases the bias and is needed for acceptable clinical accuracy. 3DE is highly feasible for visualizing the RV in an adult clinical setting.

Factors associated with development of stroke long-term after myocardial infarction: experiences from the LoWASA trial

Objective.  To describe factors associated with the development of stroke during long‐term follow‐up after acute myocardial infarction (AMI) in the LoWASA trial.

A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes

Our newly devised immunofluorometric sandwich assay for measuring plasma concentrations of activated protein C (APC) in complex with protein C inhibitor (PCI) was compared with testing for conventional markers of myocardial damage CKMB (creatine kinase MB), TNI (troponin I) and hypercoagulability (D-dimer, TAT) in 76 patients with suspected myocardial infarction (MI). APC–PCI complex levels in samples drawn on admission did not correlate with CKMB in the simultaneously drawn sample but correlated closely with maximal CKMB, which reflects MI size (r = 0.52). The areas under the receiver operating characteristics (ROC) curves calculated for the APC–PCI complex results obtained upon admission did not differ significantly from the corresponding values for CKMB, TNI or TAT. Our results show that in patients at risk for MI, the APC–PCI concentration is a sensitive and independent marker that can identify a subgroup of MI patients with normal CKMB but an increased APC–PCI level upon admission. It remains to be determined whether these patients would benefit from early intensive anticoagulant treatment.

Resistance to activated protein C due to a factor V gene mutation: The most common inherited risk factor of thrombosis

The protein C anticoagulant pathway is of major importance in maintaining vascular patency. Resistance to the key enzyme of this system, activated protein C (APC), is a recently discovered congenital defect of the protein C system. This genetic defect is present in 20% to 60% of venous thrombosis patients, making it by far the most common known pathogenetic risk factor of thrombosis. APC resistance is due to a single point mutation in the factor V gene (G to A at nucleotide position 1691) that predicts the replacement of arginine(506) by glutamine. This is associated with the loss of one of three APC cleavage sites in factor Va, one of the substrates for APC, and hypercoagulability. The identification of APC resistance as an additional genetic risk factor in a large proportion of symptomatic protein C- and protein S-deficient families has provided evidence that thrombosis is a polygenetic disease. Thus, several genetic defects act in concert with environmental factors in the pathogenesis of venous thromboembolism.

Low‐dose warfarin decreases coagulability without affecting prothrombin complex activity

Abstract. Objectives. To asses the efficacy of a fixed, low dose of warfarin in lowering factor VII coagulant activity (FVII: C) and to investigate the effects on the plasma coagulation cascade.

Comparison of different views with three-dimensional echocardiography: apical views offer superior visualization compared with parasternal and subcostal views

Studies seeking to validate real‐time three‐dimensional echocardiography (3DE) with regard to cardiac function and dimensions have almost exclusively used apical views. However, it has never been examined whether apical views are preferable to parasternal or subcostal views. In the present study, we compared the feasibility of 3DE volumetric measurements of the four heart chambers in three different views. We included 40 patients planned for a routine two‐dimensional transthoracic echocardiography examination (2DE). All patients were scanned with both 2DE and 3DE (Sonos 7500; Philips Medical Systems Andover, MA, USA). Parasternal, apical and subcostal views were used for 3DE. Volumes were calculated using manual tracing in 16 planes. 2DE was performed in parasternal longaxis, subcostal and apical four‐ and two‐chamber views. Manual tracing was used for area calculations. To be judged fully traceable, 5/6 (85%) or more of the ventricular and atrial walls had to be adequately visualized in each plane. The left ventricle and left atrium were adequately visualized in the 3DE apical view in 34 (85%) and 40 (100%) patients, respectively. Visualization of the right atrium was adequate in 31 (78%) patients, whereas the right ventricle was adequately visualized in only 12 (30%) patients. The apical view of 3DE provided superior visualization of all four heart chambers compared with the parasternal and subcostal views, when applying a slight off‐axis approach for both ventricles when needed. Thus, in the present study, there was no incremental value of assessment of chamber volumes in the parasternal and subcostal views.

Changes in levels of factor VII and protein S after acute myocardial infarction: effects of low-dose warfarin

Persistent coagulation activity after an acute myocardial infarction may increase the risk of reinfarction. We prospectively investigated the effects on plasma coagulation of a low, fixed dose of warfarin in combination with aspirin after myocardial infarction. We also evaluated the influence of coagulation activity on clinical outcome. Plasma samples from 97 patients, randomised to 1.25 mg of warfarin daily in combination with 75 mg of aspirin or aspirin alone were drawn 4 days, 1 month, and 6 months after myocardial infarction. Patients receiving warfarin had a greater reduction in factor VII coagulation activity (FVII:C) after 6 months: 0.18 vs. 0.06 U/mL,(95% CI, 0.02-0.22), whereas no differences were seen in levels of protein C, protein S, or prothrombin fragment 1+2. In the acute phase, the level of free protein S was lower than after 6 months in both groups: 25.6 vs. 28.8% (95% CI, 4.19--2.35). Cardiovascular mortality, reinfarction, and stroke were evaluated after 4 years (median). In a survival analysis, every 0.1 U/mL increase in the level of FVII:C1 month after myocardial infarction was associated with an 15% increase in risk of cardiovascular events (95% C1, 1.01-1.30). Warfarin at 1.25 mg daily reduces FVII:C but not systemic thrombin generation measured as prothrombin fragment 1 +2. Low levels of the anticoagulant protein S may contribute to a procoagulant state.

Discriminatory ability of right atrial volumes with two- and three-dimensional echocardiography to detect elevated right atrial pressure in pulmonary hypertension

Pulmonary hypertension (PH) patients have high mortality due to right ventricular failure. Predictors of poor prognostic outcome are increased right atrial volume (RAV) and elevated mean right atrial pressure (mRAP). Our aim was to determine whether RAV measured with 2D echocardiography (2DE) and 3D echocardiography (3DE) can detect elevated mRAP in patients evaluated for PH.

Changes in blood volume shunting in patients with atrial septal defects: assessment of heart function with cardiovascular magnetic resonance during dobutamine stress.

Abstract Background The purpose of this study was to determine the effect of stress on left-to-right shunting in patients with atrial septal defect (ASD) and to investigate if the degree of shunting, cardiac output (CO), and right ventricular (RV) volumes are related to exercise capacity. Methods Twenty-six patients with a secundum ASD and 16 healthy volunteers were studied with rest/stress cardiac magnetic resonance using 20 µg/kg/min dobutamine and 0.25–0.75 mg atropine to quantify CO, pulmonary to systemic flow ratio (QP/QS), and left ventricular (LV) and RV volumes. Peak oxygen uptake (VO2peak) was determined on ergospirometry. Results In patients with ASD the QP/QS decreased from 2.0 ± 0.2 at rest to 1.5 ± 0.1 (P < 0.001) during dobutamine stress (n = 20) and shunt volume per heartbeat decreased from 70 ± 9 to 38 ± 9 mL (P < 0.001). However, absolute shunt volume per minute was unchanged (5.1 ± 0.8 vs. 4.5 ± 1.0 L/min, P = 0.32) explained by a higher increase in systemic CO during stress (90 ± 11%) compared with pulmonary CO (43 ± 7%, P < 0.001). In ASD patients, VO2peak correlated with aortic CO during stress (r = 0.77) and QP/QS at rest (r = −0.48) but not during stress (P = 0.09). VO2peak did not correlate with RV volumes in patients. Conclusion Pulmonary to systemic flow ratio and shunt volume per heartbeat decrease during stress in ASD patients. This may be explained by an enhanced LV diastolic function during stress and may have implications to detect disturbances in LV compliance in ASD patients. A high systemic CO during stress is a strong predictor of exercise capacity.