NT-proBNP cut-off value for ruling out heart failure in atrial fibrillation patients - A prospective clinical study.

STUDY OBJECTIVE: N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements can be used to rule out heart failure in patients with sinus rhythm. Atrial fibrillation often coexists with heart failure but affects NT-proBNP levels. This study aims to identify the optimal NT-proBNP cut-off value for ruling out heart failure among atrial fibrillation patients. METHODS: This prospective study included 409 atrial fibrillation patients admitted to the emergency department. The inclusion criterion was documented atrial fibrillation on a 12­lead electrocardiogram. All patients completed a NT-proBNP blood sample, a chest X-ray and an echocardiogram. Heart failure was defined as a left ventricular ejection fraction of <40%. RESULTS: In total, 409 patients were included (mean age: 75.2 ± 11.6). The median NT-proBNP level was 2577 ng/L (quartiles: 1185-5438) and 21% had heart failure. We found a lower median NT proBNP level of 3187 ± 3973 ng/L in patients without heart failure compared to 9254 ± 8008 ng/L in patients with heart failure (absolute difference: 4131, 95% (CI): 3299-4986, p < 0.001). The area under the receiver operating characteristic curve for diagnosing heart failure was 0.82 (95% confidence interval: 0.77-0.87). The optimal cut-off value for ruling out heart failure was 739 ng/L with a sensitivity of 99%, a specificity of 18%, and a negative predictive value of 98%. CONCLUSIONS: NT-proBNP can be used to rule out heart failure in atrial fibrillation patients with a high negative predictive value, but low specificity. TRIAL REGISTRATION NUMBER: NCT04125966. https://clinicaltrials.gov/ct2/show/NCT04125966.

Anterior-Lateral Versus Anterior-Posterior Electrode Position for Cardioverting Atrial Fibrillation.

BACKGROUND: Smaller randomized studies have reported conflicting results regarding the optimal electrode position for cardioverting atrial fibrillation. However, anterior-posterior electrode positioning is widely used as a standard and believed to be superior to anterior-lateral electrode positioning. Therefore, we aimed to compare anterior-lateral and anterior-posterior electrode positioning for cardioverting atrial fibrillation in a multicenter randomized trial. METHODS: In this multicenter, investigator-initiated, open-label trial, we randomly assigned patients with atrial fibrillation scheduled for elective cardioversion to either anterior-lateral or anterior-posterior electrode positioning. The primary outcome was the proportion of patients in sinus rhythm after the first shock. The secondary outcome was the proportion of patients in sinus rhythm after up to 4 shocks escalating to maximum energy. Safety outcomes were any cases of arrhythmia during or after cardioversion, skin redness, and patient-reported periprocedural pain. RESULTS: We randomized 468 patients. The primary outcome occurred in 126 patients (54%) assigned to the anterior-lateral electrode position and in 77 patients (33%) assigned to the anterior-posterior electrode position (risk difference, 22 percentage points [95% CI, 13-30]; P<0.001). The number of patients in sinus rhythm after the final cardioversion shock was 216 (93%) assigned to anterior-lateral electrode positioning and 200 (85%) assigned to anterior-posterior electrode positioning (risk difference, 7 percentage points [95% CI, 2-12]). There were no significant differences between groups in any safety outcomes. CONCLUSIONS: Anterior-lateral electrode positioning was more effective than anterior-posterior electrode positioning for biphasic cardioversion of atrial fibrillation. There were no significant differences in any safety outcome. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03817372.

Maximum-fixed energy shocks for cardioverting atrial fibrillation.

AIMS: Direct-current cardioversion is one of the most commonly performed procedures in cardiology. Low-escalating energy shocks are common practice but the optimal energy selection is unknown. We compared maximum-fixed and low-escalating energy shocks for cardioverting atrial fibrillation. METHODS AND RESULTS: In a single-centre, single-blinded, randomized trial, we allocated elective atrial fibrillation patients to cardioversion using maximum-fixed (360-360-360 J) or low-escalating (125-150-200 J) biphasic truncated exponential shocks. The primary endpoint was sinus rhythm 1 min after cardioversion. Safety endpoints were any arrhythmia, myocardial injury, skin burns, and patient-reported pain after cardioversion. We randomized 276 patients, and baseline characteristics were well-balanced between groups (mean ± standard deviation age: 68 ± 9 years, male: 72%, atrial fibrillation duration >1 year: 30%). Sinus rhythm 1 min after cardioversion was achieved in 114 of 129 patients (88%) in the maximum-fixed energy group, and in 97 of 147 patients (66%) in the low-escalating energy group (between-group difference; 22 percentage points, 95% confidence interval 13-32, P < 0.001). Sinus rhythm after first shock occurred in 97 of 129 patients (75%) in the maximum-fixed energy group compared to 50 of 147 patients (34%) in the low-escalating energy group (between-group difference; 41 percentage points, 95% confidence interval 30-51). There was no significant difference between groups in any safety endpoint. CONCLUSION: Maximum-fixed energy shocks were more effective compared with low-escalating energy shocks for cardioverting atrial fibrillation. We found no difference in any safety endpoint.

Effects of hyperoxia on myocardial injury following cardioversion-A randomized clinical trial.

Oxygen has long been assumed beneficial for all ill and injured patients. However, hyperoxia may be harmful and aggravate myocardial injury such as that caused by myocardial infarction. We aimed to investigate if hyperoxia increases myocardial injury following direct current cardioversion compared with room air. METHODS: Patients undergoing elective biphasic cardioversion for atrial fibrillation or atrial flutter were randomized to receive room air or oxygen (10-15 L/min) during the procedure. The primary endpoint was the difference in high-sensitive Troponin I (hs-cTnI) and -T (hs-cTnT) measured 2 hours before and 4 hours after cardioversion. Secondary endpoints were differences in Copeptin and NT-pro-BNP. RESULTS: A total of 65 patients were randomized to high-flow oxygen (male: 71%, mean age 66.9 years) and 59 patients to room air (male: 80%, mean age 65.5 years). There was no difference in hs-cTnI between patients treated with oxygen compared to patients treated with room air (P=.09) and no significant difference for hs-cTnT, ratio 1.08 (95% CI: 0.99-1.18) (P=.09). Median hs-cTnI difference before and after cardioversion was 0.1 (interquartile range (IQR): -0.5 to 0.5) ng/L for the high-flow oxygen group and -0.3 (IQR: -1.1 to 0.4) ng/L for the room air group. There was no difference in Copeptin between patients treated with oxygen compared to room air (ratio 1.06 (95% CI: 0.89-1.27) (P=.51) or NT-pro-BNP (difference-6.0 ng/L (95% CI: -78.5 to 66.6) P=.87). CONCLUSION: Direct current cardioversion of atrial fibrillation/flutter with and without high-flow oxygen supplement was not associated with myocardial injury evaluated by high sensitive myocardial biomarkers.

Effects of renal denervation on coronary flow reserve and forearm dilation capacity in patients with treatment-resistant hypertension. A randomized, double-blinded, sham-controlled clinical trial.

BACKGROUND: Microvascular impairment is well documented in hypertension. We investigated the effect of renal sympathetic denervation (RDN) on cardiac and peripheral microvasculature in patients with treatment-resistant essential hypertension (TRH). METHODS: A randomized, single centre, double-blinded, sham-controlled clinical trial. Fifty-eight patients with TRH (ambulatory systolic BP (ASBP) ≥ 145mmHg) despite stable treatment were randomized to RDN or SHAM. RDN was performed with the unipolar Medtronic Flex catheter. Coronary flow reserve (CFR) and coronary- and forearm minimum vascular resistance (C-Rmin and F-Rmin) were determined using transthoracic Doppler echocardiography and F-Rmin with venous occlusion plethysmography at baseline and at six-months follow-up. RESULTS: RDN was performed with 5.3±0.2 lesions in the right renal artery and 5.4±0.2 lesions in the left. Baseline ASBP was 152±2mmHg (RDN, n=29) and 154±2mmHg (SHAM, n=29). Similar reductions in MAP were seen at follow up (-3.5±2.0 vs. -3.2±1.8, P=0.92). Baseline CFR was 2.9±0.1 (RDN) and 2.4±0.1 (SHAM), with no significant change at follow-up (0.2±0.2 vs. -0.1±0.2, P=0.57). C-Rmin was 1.9±0.3 (RDN) and 2.7±0.6 (SHAM) (mmHgmin/ml pr. 100g) and did not change significantly (0.3±0.5 vs. -0.4±0.8, P=0.48). F-Rmin was 3.6±0.2 (RDN) and 3.6±0.3 (SHAM) (mmHgmin/ml pr. 100ml tissue) and unchanged at follow-up (4.2±0.4 vs. 3.8±0.2, P=0.17). Left ventricular mass index was unchanged following RDN (-4±7 (RDN) vs. 3±5 (SHAM) (g/m2) P=0.38). CONCLUSION: The current study does not support positive effects of RDN on microvascular impairment in TRH.

The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial).

OBJECTIVES: To investigate, whether renal denervation (RDN) improves arterial stiffness, central blood pressure (C-BP) and heart rate variability (HRV) in patients with treatment resistant hypertension. METHODS: ReSET was a randomized, sham-controlled, double-blinded trial (NCT01459900). RDN was performed by a single experienced operator using the Medtronic unipolar Symplicity FlexTM catheter. C-BP, carotid-femoral pulse wave velocity (PWV), and HRV were obtained at baseline and after six months with the SphygmoCor®-device. RESULTS: Fifty-three patients (77% of the ReSET-cohort) were included in this substudy. The groups were similar at baseline (SHAM/RDN): n = 27/n = 26; 78/65% males; age 59 ± 9/54 ± 8 years (mean ± SD); systolic brachial BP 158 ± 18/154 ± 17 mmHg; systolic 24-hour ambulatory BP 153 ± 14/151 ± 13 mmHg. Changes in PWV (0.1 ± 1.9 (SHAM) vs. -0.6 ± 1.3 (RDN) m/s), systolic C-BP (-2 ± 17 (SHAM) vs. -8 ± 16 (RDN) mmHg), diastolic C-BP (-2 ± 9 (SHAM) vs. -5 ± 9 (RDN) mmHg), and augmentation index (0.7 ± 7.0 (SHAM) vs. 1.0 ± 7.4 (RDN) %) were not significantly different after six months. Changes in HRV-parameters were also not significantly different. Baseline HRV or PWV did not predict BP-response after RDN. CONCLUSIONS: In a sham-controlled setting, there were no significant effects of RDN on arterial stiffness, C-BP and HRV. Thus, the idea of BP-independent effects of RDN on large arteries and cardiac autonomic activity is not supported.

Elevated calprotectin in patients with atrial fibrillation with and without heart failure.

Calprotectin is an inflammatory marker, which has been found elevated in patients suffering from cardiac conditions, e.g. myocardial infarction, unstable angina and chronic heart failure. Inflammation has further been linked to atrial fibrillation (AF). However, the association between calprotectin and AF is unknown. We aimed to compare calprotectin levels in patients suffering from AF with healthy adults. In addition, AF patients with and without heart failure were compared. Calprotectin was measured in patients undergoing elective direct current cardioversion for AF. Calprotectin was determined before, 4 hours and 3 months after cardioversion. Healthy blood donors were used to verify the reference interval for calprotectin. In total, 104 prospectively enrolled patients were included. The median serum calprotectin level for AF patients was 1.6 µg/mL before cardioversion. Calprotectin levels increased significantly 4 h (1.9 µg/mL) and 3 months (2.2 µg/mL) after cardioversion. Blood donors' median serum calprotectin (1.3 µg/mL) was significantly lower than AF patients. AF patients with heart failure had significantly higher calprotectin at baseline compared with AF patients without a history of heart failure (2.0 µg/mL vs. 1.5 µg/mL). The difference was not significant at 4 h (2.0 µg/mL vs. 1.7 µg/mL) or 3 months (2.5 µg/mL vs. 2.2 µg/mL). In conclusion, the calprotectin levels in patients with AF were significantly higher than healthy blood donors and were further increased after cardioversion. AF patients with heart failure had significantly higher levels of calprotectin than AF patients without heart failure.

Cardioversion Efficacy Using Pulsed Biphasic or Biphasic Truncated Exponential Waveforms: A Randomized Clinical Trial.

BACKGROUND: Several different defibrillators are currently used for cardioversion and defibrillation of cardiac arrhythmias. The efficacy of a novel pulsed biphasic (PB) waveform has not been compared to other biphasic waveforms. Accordingly, this study aims to compare the efficacy and safety of PB shocks with biphasic truncated exponential (BTE) shocks in patients undergoing cardioversion of atrial fibrillation or -flutter. METHODS AND RESULTS: This prospective, randomized study included patients admitted for elective direct current cardioversion. Patients were randomized to receive cardioversion using either PB or BTE shocks. We used escalating shocks until sinus rhythm was obtained or to a maximum of 4 shocks. Patients randomized to PB shocks received 90, 120, 150, and 200 J and patients randomized to BTE shocks received 100, 150, 200, and 250 J, as recommended by the manufacturers. In total, 69 patients (51%) received PB shocks and 65 patients (49%) BTE shocks. Successful cardioversion, defined as sinus rhythm 4 hours after cardioversion, was achieved in 43 patients (62%) using PB shocks and in 56 patients (86%) using BTE shocks; ratio 1.4 (95% CI 1.1-1.7) (P=0.002). There was no difference in safety (ie, myocardial injury judged by changes in high-sensitive troponin I levels; ratio 1.1) (95% CI 1.0-1.3), P=0.15. The study was terminated prematurely because of an adverse event. CONCLUSIONS: Cardioversion using a BTE waveform was more effective when compared with a PB waveform. There was no difference in safety between the 2 waveforms, as judged by changes in troponin I levels. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02317029.

Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

BACKGROUND: Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. METHOD: We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). RESULTS: We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ±â€Š12 mmHg (RDN) and 159 ±â€Š14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ±â€Š18.8 mmHg (RDN) vs. -6.0 ±â€Š13.5 mmHg (SHAM)] and at 6 months [-6.1 ±â€Š18.9 mmHg (RDN) vs. -4.3 ±â€Š15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ±â€Š2.7 (RDN) vs. 7.0 ±â€Š2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. CONCLUSION: Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

[Systemic capillary leak syndrome]. / Systemisk vaskulaert laekage-syndrom.

A previously healthy 51 year-old man developed various degrees of hypovolaemia 6 times between May 2003 and November 2006. The patient was thoroughly examined for causal agents without any findings (e.g. infection, allergy, tumour, angio-oedema). Each time the patient had symptoms (nausea, diarrhoea, fatigue, oedema) and biochemistry (hypoalbuminaemia, haemoconcentration, monoclonal gammopathia) which indicated systemic capillary leak syndrome.