Meinhard Mende

Enhanced Detection of Paroxysmal Atrial Fibrillation by Early and Prolonged Continuous Holter Monitoring in Patients With Cerebral Ischemia Presenting in Sinus Rhythm

Background and Purpose Diagnosis of paroxysmal atrial fibrillation is difficult but highly relevant in patients presenting with cerebral ischemia yet free from atrial fibrillation on admission. Early initiation and prolongation of continuous Holter monitoring may improve diagnostic yield compared with the standard of care including a 24-hour Holter recording. Methods— In the observational Find-AF trial (ISRCTN 46104198), consecutive patients presenting with symptoms of cerebral ischemia were included. Patients free from atrial fibrillation at presentation received 7-day Holter monitoring. Results— Two hundred eighty-one patients were prospectively included. Forty-four (15.7%) had atrial fibrillation documented by routine electrocardiogram on admission. All remaining patients received Holter monitors at a median of 5.5 hours after presentation. In those 224 patients who received Holter monitors but had no previously known paroxysmal atrial fibrillation, the detection rate with early and prolonged (7 days) Holter monitoring (12.5%) was significantly higher than for any 24-hour (mean of 7 intervals: 4.8%, P=0.015) or any 48-hour monitoring interval (mean of 6 intervals: 6.4%, P=0.023). Of those 28 patients with new atrial fibrillation on Holter monitoring, 15 (6.7%) had been discharged without therapeutic anticoagulation after routine clinical care (ie, with data from 24-hour Holter monitoring only). Detection rates were 43.8% or 6.3% for short supraventricular runs of ≥10 beats or prolonged episodes (<5 hours) of atrial fibrillation, respectively. Diagnostic yield appeared to be only slightly and not significantly increased during the first 3 days after the index event. Conclusions— Prolongation of Holter monitoring in patients with symptoms of cerebral ischemic events increases the rate of detection of paroxysmal atrial fibrillation up to Day 7, leading to a relevant change in therapy in a substantial number of patients. Early initiation of monitoring does not appear to be crucial. Hence, prolonged Holter monitoring (≥7 days) should be considered for all patients with unexplained cerebral ischemia.

The Leipzig Prospective Vascular Ultrasound Registry in Radial Artery Catheterization: Impact of Sheath Size on Vascular Complications

OBJECTIVES This study investigated the impact of sheath size on the rate of radial artery occlusions (RAO) (primary objective) and other access site complications (hemorrhage, pseudoaneurysm, arteriovenous fistula) as secondary objectives after transradial coronary catheterization. BACKGROUND The number of vascular access complications in the published data ranges from 5% to 38% after transradial catheterization. METHODS Between November 2009 and August 2010, 455 patients 65.3 ± 10.9 years of age (62.2% male) with transradial access with 5-F (n = 153) or 6-F (n = 302) arterial sheaths were prospectively recruited. Duplex sonography was obtained in each patient before discharge. Patients with symptomatic RAO were treated with low-molecular-weight heparin (LMWH), and a follow-up was performed. RESULTS The incidence of access site complications was 14.4% with 5-F sheaths compared with 33.1% with 6-F sheaths (p < 0.001). Radial artery occlusion occurred in 13.7% with 5-F sheaths compared with 30.5% with 6-F sheaths (p < 0.001). There was no difference between groups with regard to hemorrhage, pseudoaneurysms, or arteriovenous fistulas. Female sex, larger sheath size, peripheral arterial occlusive disease, and younger age independently predicted RAO in multivariate analysis. In total, 42.5% of patients with RAO were immediately symptomatic; another 7% became symptomatic within a mean of 4 days. Of patients with RAO, 59% were treated with LMWH. The recanalization rates were significantly higher in patients receiving LMWH compared with conventional therapy (55.6% vs. 13.5%, p < 0.001) after a mean of 14 days. CONCLUSIONS The incidence of RAO by vascular ultrasound was higher than expected from previous data, especially in patients who underwent the procedure with larger sheaths.

Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial.

AIMS Remote ischaemic conditioning (RIC) and postconditioning (PostC) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in experimental and clinical ST-elevation myocardial infarction (STEMI) trials. However, their combined effects have not been studied in detail. The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control. METHODS AND RESULTS This prospective, controlled, single-centre study randomized 696 STEMI patients to one of the following three groups: (i) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention (PCI); (ii) PostC in addition to PCI; and (iii) conventional PCI (control). The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance (CMR) imaging within 3 days after infarction. Secondary endpoints included infarct size and microvascular obstruction (MVO) assessed by CMR. The combined clinical endpoint consisted of death, reinfarction, and new congestive heart failure within 6 months. The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group (49 [interquartile range 30-72] vs. 40 [interquartile range 16-68], P = 0.02). Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI (P = 0.39). The secondary endpoints, including infarct size and MVO, showed no significant differences between groups. Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups (P = 0.44). CONCLUSION Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC. CLINICALTRIALSGOV NCT02158468.

The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction

Heart failure with normal ejection fraction (HFnEF) is an important clinical entity that remains incompletely understood. The novel biomarker growth differentiation factor 15 (GDF‐15) is elevated in systolic heart failure (HFrEF) and is predictive of an adverse outcome. We investigated the clinical relevance of GDF‐15 plasma levels in HFnEF.

Steerable Versus Nonsteerable Sheath Technology in Atrial Fibrillation Ablation A Prospective, Randomized Study

Background— Steerable sheath technology is designed to facilitate catheter access, stability, and tissue contact in target sites of atrial fibrillation (AF) catheter ablation. We hypothesized that rhythm control after interventional AF treatment is more successful using a steerable as compared with a nonsteerable sheath access. Methods and Results— One hundred thirty patients with paroxysmal or persistent drug-refractory AF undergoing their first ablation procedure were prospectively included in a randomized fashion in 2 centers. Ablation was performed by 10 operators with different levels of clinical experience. Treatment outcome was measured with serial 7-day Holter ECGs and additional symptom-based arrhythmia documentation. Single procedure success (freedom from AF and/or atrial macroreentrant tachycardia) was significantly higher in patients ablated with a steerable sheath (78% versus 55% after 3 months, P=0.005; 76% versus 53% after 6 months, P=0.008). Rate of pulmonary vein isolation, procedure duration, and radiofrequency application time did not differ significantly, whereas fluoroscopy time was lower in the steerable sheath group (33±14 minutes versus 45±17 minutes, P<0.001). Complication rates showed no significant difference (3.2% versus 5%, P=0.608). On multivariable analysis, steerable sheath usage remained the only powerful predictor for rhythm outcome after 6 months of follow-up (hazard ratio, 2.837 [1.197 to 6.723]). Conclusions— AF catheter ablation using a manually controlled, steerable sheath for catheter navigation resulted in a significantly higher clinical success rate, with comparable complication rates and with a reduction in periprocedural fluoroscopy time. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00469638.

Transthoracic Echocardiography to Rule Out Paroxysmal Atrial Fibrillation as a Cause of Stroke or Transient Ischemic Attack

Background and Purpose— We assessed whether echocardiography can predict paroxysmal atrial fibrillation (PAF) in patients with cerebral ischemia presenting in sinus rhythm. Methods— Within the prospective Find-AF cohort, 193 consecutive patients with cerebral ischemia and sinus rhythm on presentation had evaluation of echocardiographic parameters of left atrial size and function. PAF was diagnosed by 7-day Holter monitoring. Results— In 26 patients with PAF, late diastolic Doppler (A) and tissue Doppler (a′) velocities were lower whereas left atrial diameter, left atrial volume index (LAVI), LAVI/A, and LAVI/a′ were larger (P<0.05 for all) than they were in 167 patients without PAF. In multivariate models A, a′, LAVI/A, and LAVI/a′ predicted the presence of PAF. Area under the receiver operating characteristic curve to diagnose PAF was highest for LAVI/a′ (0.813 [0.738; 0.889]). A previously suggested cut-off of LAVI/a′ <2.3 had 92% sensitivity, 55.8% specificity, and 98% negative predictive value for PAF. Conclusions— LAVI/a′ <2.3 can effectively rule out PAF in patients with cerebral ischemia.

Right ventricular injury in ST-elevation myocardial infarction: risk stratification by visualization of wall motion, edema, and delayed-enhancement cardiac magnetic resonance.

Background— Patients with right ventricular injury (RVI) complicating ST-elevation myocardial infarction (STEMI) have impaired prognosis, but it is unclear which patients are at risk of developing RVI. Cardiac magnetic resonance can identify these patients and might add important information on risk stratification, prognosis, and treatment. Aims were to determine the predictors and the prognostic significance of RVI assessed by wall motion abnormalities, edema, myocardial salvage index, and delayed enhancement in acute reperfused STEMI. Methods and Results— We studied 450 patients 1–4 days after primary angioplasty in STEMI. T2-weighted and delayed-enhancement cardiac magnetic resonance was used for visualizing edema and scar to calculate myocardial salvage index. Cine-imaging was performed to assess wall motion abnormalities, which, in combination with edema, were considered diagnostic for RVI. Patients with RVI were compared with matched patients with isolated left ventricular infarction. The primary end point was the occurrence of a major adverse cardiac event: a composite of death, reinfarction, and congestive heart failure after a median follow-up period of 20.9 months. RVI was present in 69 patients, and 41 of 69 showed myocardial necrosis. In a multivariable stepwise forward logistic regression analysis, a high RV myocardial mass (odds ratio, 2.06; 95% confidence interval, 1.18–3.58; P =0.012) and a low Thrombolysis In Myocardial Infarction flow before angioplasty (odds ratio, 0.50; 95% confidence interval, 0.32–0.76; P =0.011) were associated with RVI. Cox regression analysis revealed RVI as the most statistically significant predictor of time to major adverse cardiac events (hazard-ratio, 3.36; 95% confidence interval, 1.99–5.66; P <0.001). Conclusions— RVI detected by cardiac magnetic resonance is a strong and independent predictor of clinical outcome after acute reperfused STEMI. Clinical Trial Registration— URL: . Unique identifier: [NCT01359306][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01359306&atom=%2Fcirccvim%2F5%2F1%2F60.atomBackground— Patients with right ventricular injury (RVI) complicating ST-elevation myocardial infarction (STEMI) have impaired prognosis, but it is unclear which patients are at risk of developing RVI. Cardiac magnetic resonance can identify these patients and might add important information on risk stratification, prognosis, and treatment. Aims were to determine the predictors and the prognostic significance of RVI assessed by wall motion abnormalities, edema, myocardial salvage index, and delayed enhancement in acute reperfused STEMI. Methods and Results— We studied 450 patients 1–4 days after primary angioplasty in STEMI. T2-weighted and delayed-enhancement cardiac magnetic resonance was used for visualizing edema and scar to calculate myocardial salvage index. Cine-imaging was performed to assess wall motion abnormalities, which, in combination with edema, were considered diagnostic for RVI. Patients with RVI were compared with matched patients with isolated left ventricular infarction. The primary end point was the occurrence of a major adverse cardiac event: a composite of death, reinfarction, and congestive heart failure after a median follow-up period of 20.9 months. RVI was present in 69 patients, and 41 of 69 showed myocardial necrosis. In a multivariable stepwise forward logistic regression analysis, a high RV myocardial mass (odds ratio, 2.06; 95% confidence interval, 1.18–3.58; P=0.012) and a low Thrombolysis In Myocardial Infarction flow before angioplasty (odds ratio, 0.50; 95% confidence interval, 0.32–0.76; P=0.011) were associated with RVI. Cox regression analysis revealed RVI as the most statistically significant predictor of time to major adverse cardiac events (hazard-ratio, 3.36; 95% confidence interval, 1.99–5.66; P<0.001). Conclusions— RVI detected by cardiac magnetic resonance is a strong and independent predictor of clinical outcome after acute reperfused STEMI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01359306.

Excessive Supraventricular Ectopic Activity Is Indicative of Paroxysmal Atrial Fibrillation in Patients with Cerebral Ischemia

Background Detecting paroxysmal atrial fibrillation (PAF) in patients with cerebral ischemia is challenging. Frequent premature atrial complexes (PAC/h) and the longest supraventricular run on 24-h-Holter (SV-run24 h), summarised as excessive supraventricular ectopic activity (ESVEA), may help selecting patients for extended ECG-monitoring, especially in combination with echocardiographic marker LAVI/a’ (left atrial volume index/late diastolic tissue Doppler velocity). Methods Retrospective analysis from the prospective monocentric observational trial Find-AF (ISRCTN-46104198). Patients with acute stroke or TIA were enrolled at the University Hospital Göttingen, Germany. Those with sinus rhythm at presentation received 7-day Holter-monitoring. ESVEA was quantified in one 24-hour interval free from PAF. Echocardiographic parameters were assessed prospectively. Results PAF was detected in 23/208 patients (11.1%). The median was 4 [IQR 1; 22] for PAC/h and 5 [IQR 0; 9] for SV-run24 h. PAF was more prevalent in patients with ESVEA: 19.6% vs. 2.8% for PAC/h >4 vs. ≤4 (p<0.001); 17.0% vs. 4.9% for SV-run24 h >5 vs. ≤5 beats (p = 0.003). Patients with PAF showed more supraventricular ectopic activity: 29 PAC/h [IQR 9; 143] vs. 4 PAC/h [1]; [14] and longest SV-run24 h = 10 [5]; [21] vs. 0 [0; 8] beats (both p<0.001). Both markers discriminated between the PAF- and the Non-PAF-group (area under receiver-operator-characteristics-curve 0.763 [95% CI 0.667; 0.858] and 0.716 [0.600; 0.832]). In multivariate analyses log(PAC/h) and log(SV-run24 h) were independently indicative of PAF. In Patients with PAC/h ≤4 and normal LAVI/a’ PAF was excluded, whereas those with PAC/h >4 and abnormal LAVI/a’ showed high PAF-rates. Conclusions ESVEA discriminated PAF from non-PAF beyond clinical factors including LAVI/a’ in patients with cerebral ischemia. Normal LAVI/a’+PAC/h ≤4 ruled out PAF, while prevalence was high in those with abnormal LAVI/a’+PAC/h >4.

Coronary Collateral Growth Induced by Physical Exercise Results of the Impact of Intensive Exercise Training on Coronary Collateral Circulation in Patients With Stable Coronary Artery Disease (EXCITE) Trial

Background— A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear. Methods and Results— This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ⩽0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, VO2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. Conclusions— A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637.

ST-segment depression resolution predicts infarct size and reperfusion injury in ST-elevation myocardial infarction

Objective ST-elevation myocardial infarction (STEMI) is frequently associated with reciprocal ST-segment depression in contralateral ECG leads. However, the relationship of the resolution of ST-segment depression (STD-R) with myocardial damage is unknown and the potential prognostic value incompletely understood. We sought to evaluate the association between STD-R and markers of myocardial injury as well as to determine the prognostic impact of STD-R in patients with acute reperfused STEMI. Methods We enrolled 611 patients with STEMI in this multicentre cardiac magnetic resonance (CMR) study. STD-R, defined as either worsened (<0%), incomplete (0–50%) or complete (≥50%), was determined 90 min after primary percutaneous coronary intervention (PCI). Patients underwent CMR in median 3 (2–4) days after infarction. Major adverse cardiac events (MACE) were defined as a composite of death, reinfarction and new congestive heart failure within 12 months after enrolment. Results Patients with worsened or incomplete STD-R (n=148 (24.2%)) had a significantly larger area at risk (42 (31–50) vs 37 (29–52) vs 34 (24–46) %LV, p=0.001), larger infarct size (20 (13–30) vs 17(10–26) vs 16 (8–24) %LV, p=0.003), larger extent of microvascular obstruction (0.6(0–3.4) vs 0.4 (0–2.4) vs 0.0 (0–1.4) %LV, p=0.003), and a lower LVEF (46 (39–54) vs 48 (40–56) vs 52 (45–58) %, p<0.001). MACE rate (n=37 (6%)) was significantly higher in patients with worsened (n=10 (19%)) or incomplete STD-R (n=7 (7%)) than in patients with complete STD-R (n=20 (4%), p<0.001). In multivariate Cox regression analysis, categorised STD-R emerged as an independent predictor of MACE at 12 months after adjusting for clinical variables (p=0.007). Conclusions Patients with acute STEMI and worsened or incomplete STD-R after PCI show a more pronounced myocardial as well as microvascular damage as detected by CMR with subsequent independent prognostic information on MACE over a 12-month follow-up period.