Stefan Lönnerholm

The effects of aetiology on outcome in patients treated with cardiac resynchronization therapy in the CARE-HF trial

Aims Cardiac dyssynchrony is common in patients with heart failure, whether or not they have ischaemic heart disease (IHD). The effect of the underlying cause of cardiac dysfunction on the response to cardiac resynchronization therapy (CRT) is unknown. This issue was addressed using data from the CARE-HF trial. Methods and results Patients (n = 813) were grouped by heart failure aetiology (IHD n = 339 vs. non-IHD n = 473), and the primary composite (all-cause mortality or unplanned hospitalization for a major cardiovascular event) and principal secondary (all-cause mortality) endpoints analysed. Heart failure severity and the degree of dyssynchrony were compared between the groups by analysing baseline clinical and echocardiographic variables. Patients with IHD were more likely to be in NYHA class IV (7.5 vs. 4.0%; P = 0.03) and to have higher NT-proBNP levels (2182 vs. 1725 pg/L), indicating more advanced heart failure. The degree of dyssynchrony was more pronounced in patients without IHD (assessed using mean QRS duration, interventricular mechanical delay, and aorta-pulmonary pre-ejection time). Left ventricular ejection fraction and left ventricular end-systolic volume improved to a lesser extent in the IHD group (4.53 vs. 8.50% and −35.68 vs. –58.52 cm3). Despite these differences, CRT improved all-cause mortality, NYHA class, and hospitalization rates to a similar extent in patients with or without IHD. Conclusion The benefits of CRT in patients with or without IHD were similar in relative terms in the CARE-HF study but as patients with IHD had a worse prognosis, the benefit in absolute terms may be greater.

Effect of right atrial overdrive pacing in the prevention of symptomatic paroxysmal atrial fibrillation: a multicenter randomized study, the PAF-PACE study.

The aim of this study was to assess if right atrial overdrive pacing can suppress symptomatic episodes of paroxysmal atrial fibrillation (PAF) in patients without bradyarrhythmias. Forty‐two patients with frequent and symptomatic PAF without other pacing indication had a pacemaker implanted after a 4‐week run‐in period, during which the frequency of symptomatic PAF episodes and the mean heart rate were objectively documented. Depending on the mean heart rate recorded during run‐in, the pacemaker was programmed in random order to right atrial AAI pacing at 10–19 beats/min > mean heart rate (medium overdrive [MO]), at 20–29 beats/min > mean heart rate (high overdrive [HO]) and to no pacing (OAO mode) for 4–12 weeks each using a crossover design. In the 35 patients who completed the protocol, the number of symptomatic episodes of PAF (>30‐second duration) per week was significantly lower during MO pacing (median 0.88, P = 0.001, n = 35) and during HO pacing (median 0.75, P = 0.002, n = 20) than during OAO (median 2.02 and 2.04, respectively). There was no difference between MO and HO pacing in the 20 patients paced at both rates (0.97 vs 0.75, P = 0.33). Seven patients did not complete the protocol due to persistent atrial fibrillation (n = 4), angina pectoris requiring surgery (n = 1), and unwillingness to continue the study due to improvement (n = 1) or worsening (n = 1) of symptoms during the study periods. Right atrial overdrive pacing can reduce the number of symptomatic PAF episodes in patients with frequent and drug refractory PAF but without bradyarrhythmias. (PACE 2003; 26:1841–1848)

Atrial size and transport function after the Maze III procedure for paroxysmal atrial fibrillation

BACKGROUND The Maze procedure is a curative surgical therapy for atrial fibrillation, restoring sinus rhythm and improving quality of life. Because the procedure results in tissue scarring, the atrial transport function is most likely affected. METHODS Seventeen patients with paroxysmal atrial fibrillation underwent the Maze III procedure without any concomitant valve operation. Atrial size and transport function were measured before and at 2, 6, and 24 months after operations with two-dimensional echocardiography and pulsed-wave Doppler. RESULTS Fifteen patients (88%) had signs of left atrial contractions as shown by the presence of a transmitral atrial filling wave on Doppler echocardiography at 6 months follow-up. The transmitral early filling wave and atrial filling wave were measured to calculate the early filling/atrial filling wave ratio, which increased from 1.2 before to 1.9 at 2 months after the Maze procedure (nonsignificant), and further to 2.8 at 24 months (p = 0.02). A decrease in the right and left atrial size was seen at 2 months after an operation, but no further decrease occurred. CONCLUSIONS In patients with paroxysmal atrial fibrillation, there is a progressive increase in the transmitral early filling/atrial filling wave ratio after the Maze procedure, consistent with a gradual decrease in the left atrial transport function.

Long-term effects of the maze procedure on atrial size and mechanical function

BACKGROUND The Maze procedure is effective in restoring sinus rhythm, but the extensive procedure may have negative effects on atrial mechanical function. Decreased atrial contractility has been observed early after the Maze procedure. The purpose of this study was to determine the long-term effect of the Maze procedure on atrial size and mechanical function. METHODS Fifty-two patients with symptomatic atrial fibrillation, without structural heart or valvular disease, underwent the Cox Maze III procedure. Atrial size and mechanical function were assessed by echocardiographic examination at baseline and postoperatively at a mean +/- SD of 6 +/- 1 and 56 +/- 12 months. RESULTS The left atrial area was decreased 6 months after the procedure compared with baseline (mean, 15.4 +/- 3.3 vs 17.6 +/- 3.2 cm2, p < 0.01). By 56 months, however, the left atrial area had increased compared with the 6-month follow-up (19.5 +/- 3.9 vs 15.4 +/- 3.3 cm2, p < 0.001), resulting in no difference in left atrial size compared with the baseline values. The left atrial contractility, measured as fractional area change, was significantly reduced at 6 and 56 months of follow-up (0.20 +/- 0.09 and 0.19 +/- 0.07 vs baseline 0.36 +/- 0.09), as was the transmitral A-wave velocity (30 +/- 12 and 28 +/- 8 cm/s vs baseline 40 +/- 15). The same pattern was seen for the right atrium. CONCLUSIONS This study shows that the Maze procedure results in a sustained decrease in atrial contractility. The initial reduction in atrial size is later reversed. These findings contradict late improvements in atrial mechanical function after Maze surgery and may have important implications for the risk of thromboembolic complications.

Comparison of effects on coagulation and inflammatory markers using a duty-cycled bipolar and unipolar radiofrequency pulmonary vein ablation catheter vs. a cryoballoon catheter for pulmonary vein isolation

AIMS Thrombo-embolic events are one of the most feared complications related to atrial fibrillation (AF) ablation. Since radiofrequency (RF) energy is thought to be associated with a higher risk of thrombus formation than cryoenergy, the purpose of this study was to assess if the degree of activation of coagulation and inflammatory markers differed between ablation procedures performed with a cryoballoon catheter vs. a RF energy-based pulmonary vein ablation catheter (PVAC), respectively. METHODS AND RESULTS Thirty patients referred for AF ablation were randomized to pulmonary vein isolation with either the cryoballoon or the PVAC. Biomarkers were studied for endothelial damage (von Willebrand factor antigen), platelet activation (soluble P-selectin), and coagulation activity [prothrombin fragment 1 + 2 (F1 + 2) and D-dimer] at five different time points during the procedure. Troponin I (Trop I) and C-reactive protein were analysed to reflect myocardial destruction and inflammatory activity. Markers of endothelial damage and platelet activation increased after ablation in both the cryo and the RF group. Similarly, the D-dimer levels increased significantly (P = 0.001) in both groups, whereas the F1 + 2 levels increased after the transseptal puncture only (P = 0.001). The overall activation of the coagulation system was, however, comparable between the groups. The cryoballoon was associated with higher Trop I compared with the PVAC (P < 0.001), but the ratios between biomarkers and Trop I were higher with the PVAC than with the cryoballoon. CONCLUSION Even though the cryoballoon causes a higher degree of myocardial destruction than the PVAC, markers of coagulation, endothelial damage, and inflammation were comparable between the two techniques.

Autonomic denervation after the Maze procedure.

LÖNNERHOLM, S., et al.: Autonomic Denervation After the Maze Procedure. The Maze III procedure is a surgical operation for curative treatment of AF. The procedure is extensive, however, with multiple incisions in both atria, and its effects on autonomic regulation of the heart rhythm are not known. This study comprises 17 patients, 10 with paroxysmal AF and 7 with chronic AF, who had no concurrent cardiac disease known to affect heart rate variability (HRV). A 24‐hour Holter recording was performed preoperatively and 2 months (early) and 7 months (late) after surgery, for analysis of HRV in the time and frequency domains. Early after the Maze procedure all HRV components were markedly reduced compared to baseline (mean ± 1 SD): SDNN 73 ± 13 versus 148 ± 50 (ms), total power 168 ± 126 versus 560 ± 1567 (ms2), low frequency (LF) power 47 ± 67 versus 826 ± 677 (ms2), high frequency (HF) power 47 ± 40 versus 678 ± 666 (ms2), and LF:HF 1.22 ± 0.9 versus 2.55 ± 1.4 . Late after the Maze procedure all variables were still reduced. Only total power increased significantly between early and late follow‐up ( 168 ± 126 vs 496 ± 435 ms2). Late after Maze surgery, values of the different HRV components did not differ between the patients with paroxysmal AF and chronic AF. Early after the Maze procedure there is a marked decrease of all HRV components, which is maintained 7 months after surgery, a pattern consistent with denervation of the heart. (PACE 2003; 26[Pt. I]:587–592)

Acute and long-term efficacy and safety with a single cryoballoon application as compared with the standard dual application strategy: a prospective randomized study using the second-generation cryoballoon for pulmonary vein isolation in patients with symptomatic atrial fibrillation

Aims A single cryoballoon (CB) application per vein for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) could save time and was therefore compared to the standard approach of two consecutive CB applications for acute and long-term efficacy and safety. Methods and results Patients with symptomatic AF were randomized to a single CB application per vein guided by an Achieve® catheter (Single cryo-arm) or to two CB applications using a standard guidewire (Routine cryo-arm). The primary endpoint was the rate of acute complete PVI. Secondary endpoints were freedom from AF evaluated by electrocardiogram and 7 days Holter at 6 and 12 months, symptoms by Symptom Severity Questionnaires and EHRA score and quality of life (QoL) by EQ5D-5L at 12 months. Among 140 patients included, PVI was achieved in 271 (100%) veins in the Single cryo-arm and in 269/271 (99.3%) veins in the Routine cryo-arm, P = 0.25. The procedure time was shorter in the Single cryo-arm, mean ± standard deviation 99.4 ± 33.3 min vs. 118.4 ± 34.3 min, P = 0.0015. Freedom from AF after one procedure at 12 months did not differ; 73.9.0% (Single cryo) vs. 71.4% (Routine), P = 0.74. Symptoms and QoL did also not differ between the two groups. There was a lower complication rate in the Single cryo-group, 2.9% vs. 12.9%, P = 0.03. Conclusion A single CB application shortens the procedure time without affecting acute or long-term efficacy, as compared to the routine two-application strategy, which with the lower complication rates has important implications when defining standards for PVI.