Peter Søgaard

Cardiac-Resynchronization Therapy in Heart Failure with a Narrow QRS Complex

BACKGROUND Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients. METHODS We conducted a randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 msec, and echocardiographic evidence of left ventricular dyssynchrony. All patients underwent device implantation and were randomly assigned to have CRT capability turned on or off. The primary efficacy outcome was the composite of death from any cause or first hospitalization for worsening heart failure. RESULTS On March 13, 2013, the study was stopped for futility on the recommendation of the data and safety monitoring board. At study closure, the 809 patients who had undergone randomization had been followed for a mean of 19.4 months. The primary outcome occurred in 116 of 404 patients in the CRT group, as compared with 102 of 405 in the control group (28.7% vs. 25.2%; hazard ratio, 1.20; 95% confidence interval [CI], 0.92 to 1.57; P=0.15). There were 45 deaths in the CRT group and 26 in the control group (11.1% vs. 6.4%; hazard ratio, 1.81; 95% CI, 1.11 to 2.93; P=0.02). CONCLUSIONS In patients with systolic heart failure and a QRS duration of less than 130 msec, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality. (Funded by Biotronik and GE Healthcare; EchoCRT ClinicalTrials.gov number, NCT00683696.).

Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): a randomised controlled trial

BACKGROUND An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial. METHODS We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II-III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00538356. FINDINGS We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65·5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58·7%). At 1 year, 63 (18·9%) of 333 patients in the telemonitoring group versus 90 (27·2%) of 331 in the control group (p=0·013) had worsened composite score (odds ratio 0·63, 95% CI 0·43-0·90). Ten versus 27 patients died during follow-up. INTERPRETATION Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice. FUNDING Biotronik SE & Co. KG.

Cardiac Dysfunction Assessed by Echocardiographic Tissue Doppler Imaging Is an Independent Predictor of Mortality in the General Population

Background— Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown. Methods and Results— Within the Copenhagen City Heart Study, a large community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and TDI. Averages of peak systolic (s′), early diastolic (e′), and late diastolic (a′) velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas index) of diastolic and systolic performance: e′/(a′×s′). During follow-up (median, 5.3 years), 90 participants died. Left ventricular dysfunction by TDI, in terms of low s′ (hazard ratio, 1.23 per 1-cm/s decrease; P<0.05) and a′ (hazard ratio, 1.20 per 1-cm/s decrease; P=0.001), were significant predictors of death in Cox proportional-hazards models adjusted for clinical variables (age, sex, body mass index, heart rate, hypertension, diabetes mellitus, and ischemic heart disease) and conventional echocardiography. The adjusted hazard ratio for death in the third tertile compared with the first tertile of the combined index of systolic and diastolic performance by TDI was 2.5 (P<0.005). Conclusions— In the general population, in which most are free of left ventricular systolic dysfunction and restrictive diastolic filling using conventional echocardiographic parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function.

Sequential Biventricular Pacing

The study evaluated the clinical safety, performance, and efficacy of sequential biventricular pacing in the InSync III (Model 8042) biventricular stimulator in a multicenter, prospective 3‐month study and assessed the proper functioning of features aiming at improving biventricular AV therapy delivery. The system was successfully implanted in 189 (95.9%) of 198 patients with symptomatic systolic heart failure and a prolonged QRS complex duration. Patients significantly improved their 6‐minute hall walk distance (baseline 339 ± 92 vs 3‐month 422 ± 127 meter, P < 0.001) and NYHA class (baseline 3.1 ± 0.5 vs 3‐month 1.9 ± 0.7, P < 0.001). Echocardiographic optimization of sequential biventricular pacing showed an improvement in stroke volume compared to simultaneous stimulation (sequential 68 ± 24 mL vs simultaneous 56 ± 23 mL, P < 0.001) at baseline and at 3 months. In 88% (30/34) of the patients these improvements were seen within a small range of V‐V delays of ±20 ms and in 94% (32/34) within V‐V delays of ±40 ms. In contrast, programming beyond this range reduced stroke volume below that during simultaneous biventricular pacing. The device functioned as expected. LV lead dislodgement was observed in 12 patients and phrenic nerve stimulation required lead repositioning in 2 patients. Eight patients died during the study. Patient survival at 3 and 6 months was 97 ± 2% and 94 ± 2%, respectively. Cause of death was cardiac (n = 7), heart failure related (n = 3), arrhythmia related (n = 2), and unknown (n = 2). In conclusion, this sequential biventricular pacemaker was safe and efficacious. (PACE 2004; 27:339–345)

Cardiac imaging in infectious endocarditis

Infectious endocarditis remains both a diagnostic and a treatment challenge. A positive outcome depends on a rapid diagnosis, accurate risk stratification, and a thorough follow-up. Imaging plays a key role in each of these steps and echocardiography remains the cornerstone of the methods in use. The technique of both transthoracic echocardiography and transoesophageal echocardiography has been markedly improved across the last decades and most recently three-dimensional real-time echocardiography has been introduced in the management of endocarditis patients. Echocardiography depicts structural changes and abnormalities in the heart, but it does not uncover the underlying pathophysiological processes at the cellular or molecular level. This problem is addressed with introduction of new molecular imaging methods as (18)F-fluorodesoxyglucose ((18)F-FDG) PET-CT and single photon emission computed tomography fused with conventional CT (SPECT/CT). Of these methods, (18)F-FDG PET-CT carries the best promise for a future role in endocarditis. But there are distinct limitations with both SPECT/CT and (18)F-FDG PET-CT which should not be neglected. MRI and spiral CT are methods primarily used in the search for extra cardial infectious foci. A flowchart for the use of imaging in both left-sided and right-sided endocarditis is suggested.

Electromechanical Mapping for Detection of Myocardial Viability in Patients With Ischemic Cardiomyopathy

BackgroundWe evaluated the ability of electromechanical mapping of the left ventricle to distinguish between nonviable and viable myocardium in patients with ischemic cardiomyopathy. Methods and ResultsUnipolar voltage amplitudes and local endocardial shortening were measured in 31 patients (mean±SD age, 62±8 years) with ischemic cardiomyopathy (ejection fraction, 30±9%). Dysfunctional regions, identified by 3D echocardiography, were characterized as nonviable when PET revealed matched reduction of perfusion and metabolism and as viable when perfusion was reduced or normal and metabolism was preserved. Mean unipolar voltage amplitudes and local shortening differed among normal, nonviable, and viable dysfunctional segments. Coefficient of variation for local shortening exceeded differences between groups and did not allow distinction between normal and dysfunctional myocardium. Optimum nominal discriminatory unipolar voltage amplitude between nonviable and viable dysfunctional myocardium was 6.5 mV, but we observed a great overlap between groups. Individual cutoff levels calculated as a percentage of electrical activity in normal segments were more accurate in the detection of viable dysfunctional myocardium than a general nominal cutoff level. The optimum normalized discriminatory value was 68%. Sensitivity and specificity were 78% for the normalized discriminatory value compared with 69% for the nominal value (P <0.02). ConclusionsEndocardial ECG amplitudes in patients with ischemic cardiomyopathy display a wide scatter, complicating the establishment of exact nominal values that allow distinction between viable and nonviable areas. Individual normalization of unipolar voltage amplitudes improves diagnostic accuracy. Electroanatomic mapping may enable identification of myocardial viability.

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.

Left bundle-branch block: the relationship between electrocardiogram electrical activation and echocardiography mechanical contraction

BACKGROUND The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently been independently published for both ECG and echocardiography. The relationship between the 2 modalities and the relation to cardiac resynchronization therapy (CRT) response was investigated. METHODS Sixty-six patients with LBBB by conventional criteria had a standard 12-lead ECG and 2-dimensional strain echocardiography performed before CRT implantation. Criteria for LBBB by echocardiography included early termination of contraction in one wall and prestretch and late contraction in opposing wall(s). New strict criteria by ECG included QRS duration ≥140 ms (men) or 130 ms (women), QS or rS in leads V1 and V2, and mid-QRS notching or slurring in ≥2 of leads V1, V2, V5, V6, I, and aVL. Response was defined as >15% decrease in left ventricular end-systolic volume after 6 months. RESULTS In 64 of 66 patients, ECG analysis was possible. Echo and ECG readings for LBBB presence were concordant in 54 (84%) of 64. Thirty-seven (82%) of 45 patients with LBBB by strict ECG criteria responded to CRT, whereas only 4 (21%) of the 19 patients without LBBB responded (sensitivity 90% and specificity 65%). Thirty-six (95%) of 38 patients with concordance for the presence of LBBB responded to CRT. In patients with concordance for the absence of LBBB, 15 (94%) of 16 did not respond. CONCLUSION For the first time, a close relation has been demonstrated between electrical activation by ECG and mechanical contraction by echocardiography. These findings may help identify CRT candidates.

Speckle-tracking echocardiography for predicting outcome in chronic aortic regurgitation during conservative management and after surgery.

OBJECTIVES The aim of this study was to test myocardial deformation imaging using speckle-tracking echocardiography for predicting outcomes in chronic aortic regurgitation. BACKGROUND In chronic aortic regurgitation, left ventricular (LV) dysfunction must be detected early to allow timely surgery. Speckle-tracking echocardiography has been proposed for this purpose, but the clinical value of this method in aortic regurgitation has not been established. METHODS A longitudinal study was performed in 64 patients with moderate to severe aortic regurgitation. Thirty-five patients were managed conservatively with frequent clinical visits and sequential echocardiography and followed for an average of 19 ± 8 months, while 29 patients underwent surgery for the valve lesion and were followed for 6 months post-operatively. Baseline LV function by speckle-tracking and conventional echocardiography was compared with impaired outcome after surgery (defined as persisting symptoms or persisting LV dilation [LV end-diastolic volume index ≥ 87 ml/m(2)] or dysfunction [LV ejection fraction <50%]) and with disease progression during conservative management (defined as development of symptoms, increase in LV volume >15%, or decrease in LV ejection fraction >10%). RESULTS Reduced myocardial systolic strain, systolic strain rate, and early diastolic strain rate by speckle-tracking echocardiography was associated with disease progression during conservative management (-16.3% vs. -19.0%, p = 0.02; -1.04 vs. -1.19 s(-1), p = 0.02; and 1.20 vs. 1.60 s(-1), p = 0.002, respectively) and with impaired outcome after surgery (-11.5% vs. -15.6%, p = 0.01; -0.88 vs. -1.01 s(-1), p = 0.04; and 0.98 vs. 1.33 s(-1), p = 0.01, respectively). Conventional parameters of LV function and size (LV ejection fraction and LV end-diastolic volume index) were associated with outcome after surgery (p = 0.04 and p = 0.01, respectively) but not with outcome during conservative management (p = 0.57 and p = 0.39, respectively). CONCLUSIONS Speckle-tracking echocardiography is useful for the early detection of LV systolic and diastolic dysfunction in chronic aortic regurgitation.

Long-term musculoskeletal and cardiac health effects of recreational football and running for premenopausal women.

We examined long‐term musculoskeletal and cardiac adaptations elicited by recreational football (FG, n=9) and running (RG, n=10) in untrained premenopausal women in comparison with a control group (CG, n=9). Training was performed for 16 months (∼2 weekly 1‐h sessions). For FG, right and left ventricular end‐diastolic diameters were increased by 24% and 5% (P<0.05), respectively, after 16 months. Right ventricular systolic function measured by tricuspid annular plane systolic excursion (TAPSE) increased (P<0.05) in FG after 4 months and further (P<0.05) after 16 months (15% and 32%, respectively). In RG and CG, cardiac structure, E/A and TAPSE remained unchanged. For FG, whole‐body bone mineral density (BMD) was 2.3% and 1.3% higher (P<0.05) after 16 months, than after 4 and 0 months, respectively, with no changes for RG and CG. FG demonstrated substantial improvements (P<0.05) in fast (27% and 16%) and slow (16% and 17%) eccentric muscle strength and rapid force capacity (Imp30ms: 66% and 65%) after 16 months compared with 4 and 0 months, with RG improving Imp30ms by 64% and 46%. In conclusion, long‐term recreational football improved muscle function, postural balance and BMD in adult women with a potential favorable influence on the risk of falls and fractures. Moreover, football training induced consistent cardiac adaptations, which may have implications for long‐term cardiovascular health.