Patrick M. Heck

Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial.

Background— Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. Methods and Results— Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL; P=0.040). After remote IPC, cTnI was <0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%; P=0.01). Subjects who received remote IPC experienced less chest discomfort (P=0.0006) and ECG ST-segment deviation (P=0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events; P=0.018). Conclusion— Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.

DPP-4 Inhibition by Sitagliptin Improves the Myocardial Response to Dobutamine Stress and Mitigates Stunning in a Pilot Study of Patients With Coronary Artery Disease

Background—Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted postprandially that promotes myocardial glucose uptake. The active amide GLP-1 (7-36) is degraded by the enzyme DPP-4, and drugs that inhibit this enzyme (such as sitagliptin) have been introduced to treat type 2 diabetes. We assessed the hypothesis that increasing the plasma concentration of GLP-1 by DPP-4 inhibition would protect the heart from ischemic left ventricular (LV) dysfunction during dobutamine stress echocardiography in patients with coronary artery disease. Methods and Results—Fourteen patients with coronary artery disease and preserved LV function awaiting revascularization were studied. After either a single dose of 100 mg sitagliptin or placebo, 75 g of glucose was given orally to promote GLP-1 secretion and dobutamine stress echocardiography was conducted with tissue Doppler imaging at rest, peak stress, and 30 minutes. After sitagliptin, plasma GLP-1 (7-36) was increased at peak stress (16.5±10.7 versus 9.7±8.7 pg/mL; P=0.003) and in recovery (12.4±5.5 versus 9.0±5.5 pg/mL; P=0.01), and the LV response to stress was enhanced (ejection fraction, 72.6±7.2 versus 63.9±7.9%, P=0.0001; mitral annular systolic velocity, 12.54±3.18 versus 11.49±2.52 cm/s; P=0.0006). DPP-4 inhibition also improved LV regional function in the 12 paired nonapical segments assessed by peak systolic tissue Doppler (velocity, 10.56±4.49 versus 9.81±4.26 cm/s, P=0.002; strain, −15.9±6.3 versus −14.6±6.6%, P=0.01; strain rate, −2.04±1.04 versus −1.75±0.98 s−1, P=0.0003). This was predominantly due to a cardioprotective effect on ischemic segments (velocity in ischemic segments, 9.77±4.18 versus 8.74±3.87, P=0.007; velocity in nonischemic segments, 11.51±4.70 versus 11.14±4.38, P=0.14). In recovery, sitagliptin attenuated the postischemic stunning seen after the control study. Conclusions—The augmentation of GLP-1 (7-36) by inhibition of DPP-4 improves global and regional LV performance in response to stress and mitigates postischemic stunning in humans with coronary artery disease. Clinical Trial Registration—URL: http://www.isrctn.org. Unique identifier: ISRCTN78649100.

Long-term effects of catheter ablation for lone atrial fibrillation: progressive atrial electroanatomic substrate remodeling despite successful ablation.

BACKGROUND Whether curative ablation can prevent progression of the atrial electroanatomic remodeling associated with atrial fibrillation (AF) is not known. OBJECTIVE The purpose of this study was to determine whether successful radiofrequency ablation (RFA) of AF can prevent progression of the atrial substrate associated with AF. METHODS Detailed right atrial electroanatomic maps from 11 patients without apparent structural heart disease undergoing RFA of AF at baseline and ≥6 months following successful RFA were compared to 11 control patients undergoing electrophysiologic evaluation of supraventricular tachycardia. Bipolar voltage, conduction, effective refractory periods (ERPs), and signal complexity were assessed. RESULTS At baseline compared with the control group, the AF group demonstrated (1) lower voltage (P <.001); (2) slowed conduction (P = .005); (3) more prevalent complex signals (P <.001); (4) prolonged regional refractoriness (P <.05), and (5) left atrial dilation (P = .01). At 10 ± 13 month follow-up, the AF group demonstrated the following compared to baseline: (1) lower voltage (P <.05); (2) either no improvement or further slowing of conduction; (3) further prolongation of regional refractoriness (P <.05); and (4) reversal of left atrial dilation (P <.05). CONCLUSION Patients with lone AF demonstrate evidence of an abnormal atrial substrate at baseline compared to control patients without AF. This substrate does not appear to reverse even after successful catheter ablation. These findings may have implications for long-term outcomes of ablation and for timing of ablative intervention.

Predictive value of impedance changes for real-time contact force measurements during catheter ablation of atrial arrhythmias in humans

BACKGROUND Catheter-tissue contact force (CF) determines radiofrequency (RF) ablation lesion size. Impedance changes during RF delivery are used as surrogate markers for CF. The relationship between impedance and real-time CF in humans remains unknown. OBJECTIVES To determine whether impedance changes have predictive value for real-time CF during catheter ablation of atrial arrhythmias. METHODS Real-time CF, force-time integral, and impedance were measured in 2265 RF lesions for atrial fibrillation or flutter in 34 patients. Operators were blinded to CF measurements. Impedance preablation, at 5-second intervals for 30 seconds after the RF onset, maximal impedance fall and time to impedance plateau during RF were correlated with CF. Average CF was divided into low (≤20 g), intermediate (21-60 g), and high (>60 g) categories. RESULTS Preablation impedance poorly correlated with preablation CF (R = .07). Maximal impedance fall modestly correlated with average CF and force-time integral (R = .32 and .37, respectively). There was a large degree of overlap in impedance fall between different CF categories. A maximal impedance fall of 10 Ω could predict average CF of >20 g, with a sensitivity and specificity of 71% and 53% and a positive and negative predictive value of 51% and 49%, respectively. Impedance fall was only able to differentiate between different CF categories ≥15 seconds after the RF onset. Higher CFs moderately correlated with delayed plateau in impedance (R = .41). CONCLUSIONS Impedance measurements (both baseline and impedance fall) are, at best, moderately efficacious as surrogate markers for predicting real-time catheter-tissue CF. These findings highlight the importance of real-time CF measurements, rather than impedance changes to optimize ablation efficacy.

Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial electrophysiology

BACKGROUND Omega-3 polyunsaturated fatty acids in fish oils may have antifibrillatory effects. Their mechanism of action in humans is poorly understood. OBJECTIVE The purpose of this study was to investigate the effects of chronic fish oil supplementation on human atrial electrophysiology (EP). METHODS Two groups of patients without clinical AF or structural heart disease and fish intake ≤1/week were prospectively recruited into a control group (n = 30) and a fish oil group (n = 31). The latter were prescribed 6 g/day of fish oil for ≥1 month before an EP study. The following were compared at time of EP study: serum omega-3 levels; right atrial and coronary sinus effective refractory periods (ERPs); interatrial, intra-atrial, left atrial, and coronary sinus conduction at baseline and the maximal conduction delay with the shortest propagated extrastimulus; and inducibility of AF (10 inductions/patient). RESULTS The following significant differences were noted favoring the fish oil group at time of EP: (1) twofold higher total omega-3 levels (P < .001); (2) lengthening of ERPs by 8%-14% at all measured sites and pacing cycle lengths (P < .05); (3) no effect on baseline interatrial, intra-atrial, left atrial, and coronary sinus conduction but a significant attenuation of maximal conduction delay (P < .05); (4) less inducible AF (AF ≥30 seconds: 24.2% vs. 7.9%; P < .001); (5) shorter mean duration of induced AF (P = .003); and (6) prolongation of induced AF cycle length (P < .001). CONCLUSIONS Chronic fish oil supplementation in humans prolongs atrial refractoriness and reduces vulnerability to inducible AF. These EP changes may explain the antifibrillatory effect of chronic fish oil ingestion.

Implantable cardioverter-defibrillators in the elderly: rationale and specific age-related considerations

Despite the increasingly high rate of implantation of cardioverter-defibrillators (ICD) in elderly patients, data supporting their clinical and cost-effectiveness in this age stratum are ambiguous and contradictory. We comprehensively reviewed the state-of-the-art data regarding the applicability, safety, clinical- and cost-effectiveness of the ICD in elderly patients, and analysed which patients in this age stratum are more likely to get a survival benefit from this therapy. Although peri-procedural risk may be slightly higher in the elderly, this procedure is still relatively safe in this age group. In terms of correcting potentially life-threatening arrhythmias, the effectiveness of ICD therapy is comparable in older and younger individuals. However, the assumption of persistent ICD benefit in the elderly population is questionable, as any advantage of the device on arrhythmic death may be largely attenuated by a higher total non-arrhythmic mortality. While septuagenarians and octogenarians have higher annual all-cause mortality rates, ICD therapy may remain effective in highly selected patients at high risk of arrhythmic death and with minimum comorbidities despite advanced age. ICD intervention among the elderly, as a group, may not be cost-effective, but the procedure may reach cost-effectiveness in those expected to live >5-7 years after implantation. Biological age rather than chronological age per se should be the decisive factor in making a decision on ICD selection for survival benefit.

Relationship among complex signals, short cycle length activity, and dominant frequency in patients with long-lasting persistent AF: a high-density epicardial mapping study in humans.

BACKGROUND Complex fractionated atrial electrograms (CFAEs) and regions of high dominant frequency (DF) both may identify sites critical to the maintenance of atrial fibrillation (AF). CFAEs may be defined by either (1) complex multicomponent electrograms (EGMs) and/or continuous electrical activity (multicomponent/continuous EGM) or (2) discrete high-frequency EGMs. OBJECTIVE The purpose of this study was to test if the 2 definitions of CFAE identify the same arrhythmia substrate and determine the relationship of CFAE to areas of high DF. METHODS High-density epicardial mapping of the posterior left atrium was performed in 10 patients with long-lasting persistent AF. Point-by-point analysis was performed to determine the spatial distribution and correlation of CFAE defined as either (1) multicomponent/continuous-EGMs or (2) AF cycle length <120 ms. Additionally, spatial analysis was performed to determine the relationship of high DF sites to CFAE sites defined by each of the 2 definitions. RESULTS The percentage of sites deemed CFAE varied markedly between patients and was different depending on the definition of CFAE adopted. There was a poor correlation between CFAE defined by multicomponent/continuous EGMs and AF cycle length <120 ms (r = 0.18). High DF sites were arranged in clusters evenly distributed throughout the posterior left atrium, with 4.2 ± 1.0 high DF clusters per patient. Although there was poor point-by-point correlation between multicomponent/continuous EGMs and high DF sites (r = 0.107), spatial analysis revealed that 96% of multicomponent/continuous EGMs were found adjacent to and partially surrounding (≤5 mm) high DF sites. CONCLUSION There is poor anatomic overlap between CFAE defined by multicomponent/continuous EGMs and CFAE defined by AF cycle length <120 ms. Multicomponent/continuous EGMs are found adjacent to and surrounding sites of high DF. Further studies are needed to determine the mechanisms responsible for these different signals.

Remote ischaemic pre‐conditioning does not attenuate ischaemic left ventricular dysfunction in humans

Remote ischaemic pre‐conditioning (RIPC) reduces distant tissue ischaemia reperfusion injury. We tested the hypothesis that RIPC would protect the left ventricle (LV) from ischaemic dysfunction and stunning.

Remote Ischemic Preconditioning Stimulus Does Not Reduce Microvascular Resistance or Improve Myocardial Blood Flow in Patients Undergoing Elective Percutaneous Coronary Intervention

Introduction: Remote ischemic preconditioning (RIPC) may limit myocardial infarction by improving microvascular function and maintaining myocardial blood flow. We hypothesized that a RIPC stimulus would reduce coronary microvascular resistance and improve coronary blood flow during elective percutaneous coronary intervention (PCI). Method: We prospectively recruited 54 patients with multi-vessel disease (MVD = 32) or single vessel disease awaiting elective PCI. Patients with MVD had non-target vessel (NTV) index of micro-circulatory resistance (IMR) determined, before and after target vessel (TV) PCI (cardiac RIPC). The effect of arm RIPC on serial microvascular resistance (Rp) was assessed in patients with single vessel disease. Results: TV balloon occlusion did not alter the NTV IMR: 16.5 (12.4) baseline vs. 17.6 (11.6) post cardiac RIPC, P = 0.65 or hyperaemic transit time. Arm RIPC did not alter R p in patients with single vessel disease: Rp, mmHg.cm-1.s -1: 3.5 (1.9) baseline vs. 4.1 (3.0) post arm RIPC, P = 0.19 and coronary flow velocity remained constant. Conclusion: RIPC stimuli during elective PCI do not affect coronary microvascular resistance or coronary flow in humans.

Effects of Chronic Omega-3 Polyunsaturated Fatty Acid Supplementation on Human Pulmonary Vein and Left Atrial Electrophysiology in Paroxysmal Atrial Fibrillation

Omega-3 polyunsaturated fatty acids in fish oils may have antifibrillatory effects; however, their electrophysiologic effects in paroxysmal atrial fibrillation (PAF) remain unknown. The aim of this study was to investigate the effects of chronic fish oil supplementation on human pulmonary vein (PV) and left atrial electrophysiology in PAF. Patients with PAF undergoing PV isolation were randomized ≥1 month before their procedure into a control group (n = 18) or a fish oil group (n = 18) in an unblinded fashion. The latter were supplemented with fish oil 6 g/day for a mean of 40 ± 12 days. Pulmonary venous and left atrial effective refractory periods (ERPs), PV conduction, and susceptibility to AF initiated within PVs were assessed. Compared to the control group, the fish oil group had (1) longer left-sided (p = 0.002) and right-sided (p = 0.001) pulmonary venous ERPs; (2) less dispersion of pulmonary venous ERPs (left PVs p = 0.001, right PVs p = 0.07); (3) longer left atrial ERPs (p = 0.02); (4) no difference in pulmonary venous conduction; (5) lower incidence of AF initiated from PVs during ERP testing (77% vs 31%, p = 0.02); and (6) prolongation of mean AF cycle length (p = 0.009) and shortest AF cycle length in PVs (p = 0.04). In conclusion, patients with PAF chronically supplemented with fish oils exhibit distinctive electrophysiologic properties including prolonged pulmonary venous and left atrial ERPs and decreased susceptibility to initiation AF from within PVs. These changes may in part explain the antifibrillatory effect of chronic omega-3 polyunsaturated fatty acid supplementation in patients with PAF.