Anders Sahlén

Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry.

AIMS Ticagrelor reduces ischaemic events and mortality in acute coronary syndrome (ACS) vs. clopidogrel. We wished to study clinical outcomes in a large real-world population post-ACS. METHODS AND RESULTS We performed a prospective cohort study in 45 073 ACS patients enrolled into Swedish Web system for Enhancement and Development of Evidence-based care in Heart Disease Evaluated According to Recommended Therapies who were discharged on ticagrelor (N = 11 954) or clopidogrel (N = 33 119) between 1 January 2010 and 31 December 2013. The primary outcome was a composite of all-cause death, re-admission with myocardial infarction (MI) or stroke, secondary outcomes as the individual components of the primary outcome, and re-admission with bleeding. The risk of the primary outcome with ticagrelor vs. clopidogrel was 11.7 vs. 22.3% (adjusted hazard ratio (HR) 0.85 [95% confidence interval: 0.78-0.93]), risk of death 5.8 vs. 12.9% (adjusted HR 0.83 [0.75-0.92]), and risk of MI 6.1 vs. 10.8% (adjusted HR 0.89 [0.78-1.01]) at 24 months. Re-admission with bleeding with ticagrelor vs. clopidogrel occurred in 5.5 vs. 5.2% (adjusted HR 1.20 [1.04-1.40]). In a subset of patients undergoing percutaneous coronary intervention (PCI) on ticagrelor vs. clopidogrel the PCI-related in-hospital bleeding was 3.7 vs. 2.7% (adjusted odds ratio, OR, 1.57 [1.30-1.90]). CONCLUSION Ticagrelor vs. clopidogrel post-ACS was associated with a lower risk of death, MI, or stroke, as well as death alone. Risk of bleeding was higher with ticagrelor. These real-world outcomes are consistent with randomized trial results.

Cardiac fatigue in long-distance runners is associated with ventricular repolarization abnormalities

BACKGROUND Prolonged exercise can induce cardiac fatigue, which is characterized by biomarker release and impaired myocardial function. The impact on ventricular electrophysiology is largely unknown. OBJECTIVE The objective of this study was to examine changes in ventricular repolarization after a 30-km cross-country race in runners aged >or=55 years. METHODS Fifteen healthy participants (62 +/- 5 years) were assessed using biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], troponin T [TnT]), tissue Doppler echocardiography, and vectorcardiography at baseline, within 1 hour postrace and on days 1 and 6 postrace. RESULTS During the race, NT-proBNP increased from 42 ng/L (interquartile range 25-117) to 187 ng/L (113-464), and TnT increased from undetectable levels to 0.03 microg/L (0.015-0.05). Global strain (19.1% +/- 2.2%) decreased on day 1 (17.2% +/- 1.8%) and day 6 (17.9% +/- 1.5%; P <.01). QT(c) increased from 431 +/- 15 ms prerace to 445 +/- 22 ms postrace and 445 +/- 15 ms on day 1 (P <.05), mainly because of an increased T(peak-end) interval (prerace 108 +/- 13 ms, postrace 127 +/- 43 ms, day 1 127 +/- 43 ms; P <.05). Postrace, T(area) (baseline 75 +/- 26 microVs) peaked on day 1 (105 +/- 42 microVs) and remained high on day 6 (89 +/- 37 microVs; P <.05). Runners with higher baseline NT-proBNP developed greater impairment of myocardial velocities (rho = -0.68 to -0.54; P <.05) and a larger increase in T(area) (rho = 0.73; P <.01). CONCLUSION Cardiac fatigue induced by prolonged exertion is associated with sustained abnormalities in ventricular repolarization. Runners with higher baseline NT-proBNP are especially liable to such alterations of cardiac function.

Predisposing Factors and Consequences of Elevated Biomarker Levels in Long-Distance Runners Aged >55 Years

Cardiac biomarkers play an important role in the diagnosis of cardiovascular disease. Elevated levels can be seen in the context of strenuous exercise. We studied this phenomenon in senior endurance runners. We included 185 participants (61.1 +/- 5 years; 29% women) at a 30-km cross-country race who were self-reportedly in excellent health. Before and after the race, the creatinine, N-terminal pro-brain natriuretic peptide (NT-proBNP), and troponin T were analyzed, and participation in the number of previous races and the race duration were recorded. NT-proBNP increased from 53 ng/L (interquartile range 31 to 89) to 121 ng/L (interquartile range 79 to 184) and troponin T from undetectable to 0.01 microg/L (interquartile range 0.01 to 0.04). The independent predictors of a large NT-proBNP increase were (1) greater levels present at baseline, (2) a greater increase in creatinine (both p <0.001), (3) older age (p = 0.01), and (4) a longer race duration (p <0.05). Troponin T elevation was independently predicted by (1) older age (p = 0.01), (2) a greater increase in creatinine, and (3) participation in fewer previous races (both p <0.05). Of the 15 runners with an elevated (>194 ng/L) baseline NT-proBNP level (8.1% of 185), 4 were found to have serious cardiovascular disease (2.2% of whole sample). Of these 4 patients, 1 died from sudden cardiac death within months after the race. In conclusion, biomarker elevation occurs commonly in senior runners. A high baseline NT-proBNP is predictive of a large release during exercise, suggesting that the factors that control the at rest levels also determine its release with exertion. Troponin T elevation was seen in less-experienced participants. A small group of very ill runners were identified by NT-proBNP analysis.

Performance trends and cardiac biomarkers in a 30-km cross-country race, 1993-2007.

PURPOSE Long-distance running events enjoy increasing popularity in all ages. Whereas the health benefits of regular moderate exercise are undisputed, the net health effects of single or repeated participation in endurance events of marathon type remain to be determined. We wanted to investigate performance trends over time and the relationship between race performance and cardiac biomarker levels among participants in a large annual 30-km cross-country race. METHODS We analyzed a database containing age, gender, run times, and previous race participation of 124,608 runners finishing the Lidingöloppet (30 km) between 1993 and 2007. In 249 male runners age ≥ 45 yr, we also performed a thorough cardiovascular examination, including measuring the cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin. RESULTS Total participation increased 56% with the largest gains in younger female and older male runners. Mean run times rose from 164 ± 27 min in 1993 to 184 ± 33 min in 2007 (P < 0.001) in men and from 179 ± 26 to 203 ± 32 in women (P < 0.001) after a strong linear relationship (men, r = 0.98; women, r = 0.93). Increased run times were seen in the mean, top, and bottom quartiles as well as in the top and bottom 5% of all age and gender groups. In the substudy among 249 older male runners, not only higher body mass index, older age, and fewer previous race participations but also higher baseline NT-proBNP was independently associated with increased run time. CONCLUSIONS Whereas participation in the Lidingöloppet increased, fitness deteriorated over time in both genders and in all ages. In a subset of older male athletes, longer run times were associated with higher levels of NT-proBNP. The present findings may support the usefulness of preparticipation evaluation to ensure appropriate fitness and cardiovascular health in long-distance race participants.

Contemporary use of ticagrelor in patients with acute coronary syndrome : insights from Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)

AIMS The platelet inhibitor ticagrelor is strongly recommended during 12 months post-acute coronary syndrome (ACS) in European guidelines. We analysed clinical characteristics of patients given ticagrelor for ACS in the real world. METHODS AND RESULTS We studied the use of ticagrelor in patients admitted for ACS in Sweden between 1 January 2012 and 31 December 2013 who were enrolled in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Clinical characteristics were investigated for patients prescribed ticagrelor at discharge as well as for patients undergoing percutaneous coronary intervention who were prescribed ticagrelor. Independent factors associated with selecting ticagrelor were analysed in logistic regression. We found that 44.0% (n = 12 601) out of a total of 28 639 patients had been prescribed ticagrelor at discharge. After adjusting for age and sex, prior cardiovascular disease was less common in patients discharged on ticagrelor (myocardial infarction, ischaemic stroke, and peripheral vascular disease; P for all <0.001). The risk of death as predicted by GRACE score and the risk of major bleeding as predicted by CRUSADE score were both lower in ticagrelor-treated patients vs. others (median 99 vs. 126 and median 23 vs. 25, respectively; P for both < 0.001). The intended treatment duration at discharge was 12 months in 82.5% of patients and <12 months in 9.3%. CONCLUSION Ticagrelor is preferentially being used in patients at lower risk. A minority of patients are recommended ticagrelor during <12 months.

Transesophageal echocardiography measurements of aortic annulus diameter using biplane mode in patients undergoing transcatheter aortic valve implantation

BackgroundAortic stenosis (AS) is a relevant common valve disorder. Severe AS and symptoms and/or left ventricular dysfunction (EF <50%) have the indication for aortic valve replacement (AVR). Majority of the patients with AS are elderly often with co-morbidities and generally have high preoperative risk. Transcatheter aortic valve implantation (TAVI) is offered in this group. Four different sizes of Corevalve prosthesis are available. Correct measurement of aortic size prior to TAVI is of great important to choose the right prosthesis size to avoid among others paravalvular leak or prosthesis patient mismatch.Aim of the study is to assess the aortic annulus diameter in patients undergoing TAVI by biplane (BP) mode using transesophageal echocardiography (TEE) and compare it to two-dimensional (2D) transthoracic echocardiography (TTE) and 2DTEE using three-dimensional (3D) TEE as reference method.MethodsThe study population consisted of 50 patients retrospectively (24 men and 26 women, mean age 85±8 years of age) who all had undergone echocardiography examination prior to TAVI.ResultsThe mean aortic annulus diameter was 20.4±2.2 mm with TTE, 22.3±2.5 mm with 2DTEE, 22.9±1.9 mm with BP-mode and 23.1±1.9 mm with 3DTEE. TTE underestimated the mean aortic annulus diameter in comparison to transesophageal imaging modalities (p<0.001). Using 3DTEE, 2% of patients were unsuitable for TAVI due to a too-small AoA (n=1). This figure was similar with BP (4%, n=2; p=1.00) but considerably larger with 2DTTE (36%, n=18; p < 0.001) and 2DTEE (12%, n=6; p=0.06). There was a strong correlation between BP-mode and 3DTEE for assessment of aortic annulus diameter (r-value 0.88) with small mean difference (−0.2±0.9 mm) whereas the other modalities showed larger 95% confidence interval and modest correlation (2DTTE vs. 3DTEE, –6.3 to 0.9 mm, r=0.64 and 2DTEE vs. 3DTEE, –4.8 to 3.2 mm, r=0.61).ConclusionA multi-dimensional method is preferred to assess aortic annulus diameter in TAVI patients since there is risk of underestimation using single plane. Biplane mode is the method of choice in view of speedy post-processing with no need for expensive dedicated software. Lastly, single plane methods lead to misclassification of patients as unsuitable for TAVI. This may be of major clinical importance.

Cardiac output response to changes of the atrioventricular delay in different body positions and during exercise in patients receiving cardiac resynchronization therapy

AIMS The aim of this study was to study the haemodynamic effect of atrioventricular delay (AVD) modifications within a narrow range in different body positions and during exercise in patients receiving cardiac resynchronization therapy (CRT). METHODS The previously optimized AVD was shortened and prolonged by 40 ms in 27 CRT patients and 9 controls without heart failure. Cardiac output (CO) was measured by inert gas rebreathing (Innocor) as the average over different body positions (left-lateral, supine, sitting, standing, and exercise). In eight CRT patients with an implantable haemodynamic monitor, the estimated pulmonary artery diastolic pressure (ePAD) was analysed. RESULTS The magnitude of CO response to AVD changes was greater in CRT patients than in controls (0.25 vs. 0.20 L/min, P<0.05), varied substantially between individuals (range: 0.12-0.56 L/min), and correlated with left atrial size (r=0.61, P<0.001). On average, AVD shortening decreased CO slightly (0.07+/-0.17 L/min) and increased ePAD (1.1+/-0.8 mmHg, both P<0.05), whereas prolongation had no significant effect. CONCLUSION The haemodynamic response to AVD modifications within a narrow range is larger in CRT patients than in normal controls and varies substantially between individuals. These findings suggest that optimal AVD tuning is clinically important in selected patients.

Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients

Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 ± 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve (NoRes; reserve <15%; n = 10) showed decreased arterial compliance during exercise, while patients with SV reserve ≥15% (Res; n = 11) showed increased compliance. Exercise produced parallel increases in LV end-diastolic volume and arterial volume in Res patients while NoRes patients exhibited a lesser decrease in SVR and a drop in effective arterial volume. Poor SV reserve in elderly female hypertensives is due to simultaneous failure of LV preload and arterial vasodilatory reserves. Abnormal arterial function contributes to a high risk of HFpEF in these patients.

Two-Dimensional Color Doppler Echocardiography for Left Ventricular Stroke Volume Assessment: A Comparison Study with Three-Dimensional Echocardiography

Aim: Whether measurement of left ventricular outflow tract diameter (LVOTd) using color Doppler (CD) in order to more accurately define LVOTd is more accurate for determination of stroke volume (SV) than gray scale and compare it with direct measurement of LVOT area (a) using three‐dimensional echocardiography (3DE) for SV determination. Methods and Results: Twenty‐one volunteers were examined. LVOTa was calculated by two‐dimensional echocardiography (2DE) using the following formula: π× (d/2)2, d = LVOT diameter by gray scale and CD, respectively. Planimetry of LVOTa was performed in parasternal long axis using 3DE. Eccentricity Index was calculated using the lateral and anterior‐posterior LVOTd. SV was obtained by four different methods: (1) 2D gray scale, (2) 2D color, (3) LVOTa × LVOT velocity time integral, and (4) SV by Simpsons biplane method. Gray scale LVOTd was significantly smaller compared to LVOTd obtained with CD (P < 0.05). Significant differences occurred between LVOTa gray scale and CD (3.29 ± 0.74 cm2 vs 3.67 ± 0.70 cm2, P < 0.05) and between LVOTa calculated by gray scale in comparison to 3DE planimetry; (3.29 ± 0.74 cm2 vs 3.61 ± 0.89 cm2, P = 0.011). Half of the subjects had at least 17% difference between the lateral and anterior‐posterior LVOTd. There were significant differences between SV by 2D gray scale and 2D CD (82.8 ± 17.1 mL vs 92.4 ± 16.8 mL, P < 0.05) and between 2D gray scale and 3DE planimetry (82.8 ± 17.1 mL vs 90.7 ± 19.8 mL, P = 0.025). Conclusion: Our study demonstrates LVOT being frequently elliptical. SV and LVOTa were found to be similar when comparing 2DE CD and 3DE planimetry and showed higher values in comparison to 2DE gray scale, which suggests 2DE CD to be an alternative approach for SV assessment.

The value of E/Em ratio in the estimation of left ventricular filling pressures: impact of acute load reduction: a comparative simultaneous echocardiographic and catheterization study.

BACKGROUND The ratio of the early transmitral flow velocity to the early diastolic tissue velocity (E/Em) has been suggested as a reliable estimate of left ventricular diastolic pressures (LVDP). However, the evidence regarding the ability of E/Em to detect LVDP changes is relatively equivocal. Our aim was to evaluate the validity of the ratio following acute load reduction. METHODS AND RESULTS 68 consecutive patients referred for coronary angiography underwent LV catheterization and echocardiography simultaneously. Doppler signals of transmitral flow and spectral TD signals at the level of the mitral annulus were obtained before and directly after intravenous administration of nitroglycerin (NTG). The predictive ability of E/Em to identify elevated LVDP was modest (area under curve=0.71 ± 0.08, p<0.01). The index was more strongly associated with LVDP in patients with reduced ejection fraction (EF)<55% (r=0.68; p<0.01) than in patients with normal EF. Following NTG, E/Em lacked any predictive potential for elevated LVDP whereas changes LVDP could not be reliably tracked using E/Em. CONCLUSION The predictive capacity of E/Em for elevated LVDP was weak and declined significantly following acute reduction in LV load. Changes in LVDP were not reliably predicted by E/Em. The current findings derived from a real-world patient population with relatively high filling pressures indicate that E/Em may not be sufficiently robust to be employed as a single non-invasive estimate of LVDP nor for monitoring load reducing medical therapy.