Radial strain imaging-guided lead placement for improving response to cardiac resynchronization therapy in patients with ischaemic cardiomyopathy: the Raise CRT trial.

AIMS: To evaluate the benefit of speckle tracking radial strain imaging (STRSI)-guided left ventricular (LV) lead (LVL) positioning in cardiac resynchronization therapy (CRT) in patients (pts) with ischaemic cardiomyopathy with CRT indication. METHODS AND RESULTS: We conducted a prospective randomized controlled trial. Patients were enrolled in nine centres with 2:1 randomization into two groups (guided vs. control). Patients underwent STRSI to identify the optimal LV position from six LV segments at midventricular level. Implantation via STRSI was attempted for recommended segment in the guided group only. Follow-up included echocardiography (6 months) and clinical evaluation (6 and 12 months). The primary endpoint was comparison % reduction in LV end-systolic volume at 6 months with baseline. Secondary endpoints included hospitalizations for heart failure and death, and improvement in additional echocardiographic measurements and quality of life score. A total of 172 patients (115 guided vs. 57 control) were enrolled. In the guided group, 60% of the implanted LV leads were adjudicated to be successfully located at the recommended segment, whereas in the control group 44% reached the best STRSI determined segment. There was no difference between the groups in any of the primary or secondary endpoints at 6 and 12 months. CONCLUSION: Our findings suggest that echo-guided implantation of an LV lead using STRSI does not improve the clinical or echocardiographic response compared with conventional implantation.

"Preventive" pacing in patients with tachy-brady syndrome (TBS): Confirming a common practice.

AIMS: Many tachy-brady syndrome (TBS) patients, are implanted a permanent pacemaker (PPM) to allow continuation of anti-arrhythmic drug (AAD) therapy to maintain sinus rhythm. Many of these PPM's are implanted as a preventive measure, in absence of symptomatic bradycardia. Our primary aim was to evaluate pacing use among these patients and find predictors for PPM use. Our secondary aim was to appreciate the portion of these patients who progress to permanent atrial fibrillation (AF). METHODS: Retrospective study of TBS patients implanted a PPM as preventive measure, dividing cases into defined categories regarding highest percent atrial and ventricular pacing documented in PPM clinic visits during 3 year follow-up (F/U) period. Patients' baseline characteristics and AAD therapy were compared between cases with a major (>90%) pacing use and cases with <90% pacing use to find predictors for pacing use. Multivariable logistic regression was applied to identify independent variables associated with major pacing use. RESULTS: Our study included 119 TBS patients. Most (86.5%) TBS patients had a moderate (>50%) pacing use and 58% had a major pacing use. Significant association was found between pre-implant severe sinus bradycardia (<40 bpm), first degree atrioventricular block and amiodarone treatment to major pacing use on univariate analysis and severe sinus bradycardia was significantly associated with major pacing on multivariate analysis as well. Only minority (16.8%) of TBS patients progressed to permanent AF during the study F/U period. CONCLUSION: Our study reveals most TBS patients succeed to maintain sinus rhythm using an AAD with a significant pacing use, suggesting preventive PPM implantation might be advantageous in these cases. Pre-implant severe sinus bradycardia (<40 bpm) is a possible predictor for major pacing use in this population.

The management of cardiac implantable electronic device lead perforations: a multicentre study.

AIMS: Lead perforation is a rare, well-known complication of cardiac implantable electronic device (CIED) implants, whose management is mostly not evidence-based. Main management strategies include conservative approach based on clinical and lead function follow-up vs. routine invasive lead revision approach. This study compared the complications of both strategies by composite endpoint, including recurrent perforation-related symptoms, recurrent pericardial effusion (PEf), lead dysfunction, and device infection during 12 month follow-up. METHODS AND RESULTS: Multicentre retrospective analysis, inquiring data from imaging studies, device interrogation, pericardiocentesis, and clinical charts of patients with suspected perforating leads between 2007 and 2014 in five hospitals. All cases were reviewed by electrophysiologist and defined as definite perforations by suggestive symptoms along with lead perforation on imaging, bloody PEf on pericardiocentesis shortly after implant, or right ventricular (RV) lead non-capture along with diaphragmatic stimulation upon bipolar pacing. Clinical outcomes associated with both management approaches were compared, with respect to the composite endpoint. The study included 48 definitive perforation cases: 22 managed conservatively and 26 via lead revision. Conservative management was associated with an increased composite endpoint compared with lead revision (8/22 vs. 1/26; P = 0.007). The dominant complication among the conservative cohort was appearance of cardiac tamponade during follow-up; 5/6 occurring in cases which presented with no or only mild PEf and were treated by antiplatelets/coagulants during or shortly after CIED implantation. CONCLUSION: A conservative management of CIED lead perforation is associated with increased complications compared with early lead revision. Lead revision may be the preferred management particularly in patients receiving antiplatelets/coagulants.

Cryoballoon-Induced Circumferential Pulmonary Vein Fibrosis, Assessed by Late Gadolinium-Enhancement Cardiac Magnetic Resonance Imaging, and Its Correlation with Clinical Atrial Fibrillation Recurrence.

BACKGROUND: Prior studies evaluating post-atrial fibrillation (AF) ablation pulmonary vein (PV) ostial gaps via magnetic resonance imaging (MRI) have shown circumferential PV fibrosis in a minority of patients, and their correlation with AF recurrence was weak. These studies were mostly based on radio-frequency AF ablations. AIM: We aimed to assess cryoballoon ablation-induced PV fibrosis via MRI and its correlation with AF recurrence. METHODS AND RESULTS: This was a prospective study of consecutive patients with symptomatic AF who underwent pre- and post-ablation MRI to assess baseline and ablation-induced fibrosis, respectively. Post-ablation PV gaps were assessed by new semi-quantitative visual analysis assisted by computerized ADAS analysis. AF recurrence monitored via multiple ECGs and event monitoring at 6 and 12 months post ablation. Nineteen patients with 80 PVs were included, age 56 ± 11, with paroxysmal and persistent AF in 17/19 and 2/19 patients, respectively. Baseline MRI showed minimal LA fibrosis. All patients underwent successful cryoballoon PV electrical isolation. Post-ablation MRI revealed circumferential PV fibrosis among 63/80 (78.8%) PVs and partial fibrosis with major gaps among 17/80 (21.2%) PVs. AF recurred within one year in 5/9 (55.5%) patients with partial PV fibrosis, while no AF recurred among the 10 patients in whom all PVs had circumferential fibrosis (p < 0.01). Similarly, there were significantly more PVs without circumferential fibrosis (due to major gaps) among patients with AF recurrence as compared with patients without AF recurrence (42.9% vs. 13.5%; p < 0.01). CONCLUSION: Cryoballoon AF ablation results in circumferential PV fibrosis in the majority of PVs, as assessed by a new clinically relevant MRI-LGE analysis. Significant correlation was found between major PV gaps on post-ablation MRI and AF recurrence, suggesting that MRI might have the ability to predict AF recurrence.

Delayed prolongation of the QRS interval in patients with left ventricular dysfunction.

AIMS: Patients with left ventricular dysfunction (LVD) and prolonged QRS on surface electrocardiogram are at increased risk for heart failure and death and may benefit from resynchronization therapy. Patients with initial narrow QRS may prolong their QRS during the disease course. The occurrence of delayed QRS prolongation, its predictors and associated risk of heart failure hospitalizations (HFH) or death are currently unknown and the subject of this investigation. METHODS & RESULTS: Patients with LVD, QRS < 120 ms and available follow-up ECGs were retrospectively evaluated for persistent unprovoked QRS prolongation >130 ms. Impact on mortality or HFH was assessed using Cox regression with QRS > 130 ms as a time dependent covariate. Following 178 patients for 30 (10;59) median (IQR) months, 28 (16%) patients prolonged their QRS to >130 ms, reaching a QRS duration of 154 ±â€¯29 ms; LBBB pattern was diagnosed among 14 (50%) patients. Patients with delayed QRS prolongation were older (71.9 ±â€¯11.8 vs 64.4 ±â€¯15.1 years p = 0.014), had larger left ventricle and left atrial diameters (6.3 ±â€¯0.9 vs 5.7 ±â€¯0.9 cm p = 0.010; 4.9 ±â€¯0.6 vs 4.5 ±â€¯0.7 cm p = 0.006, respectively) and wider baseline QRS (104.8 ±â€¯12.6 vs 91.4 ±â€¯14.5 ms p < 0.001) which was linearly associated with late QRS prolongation (p for trend<0.0001). In a multivariable model, age, baseline QRS width and left atrial diameter were significantly associated with delayed QRS prolongation. QRS prolongation at follow-up was independently associated with risk of death or HFH (HR 7.426, 95% CI3.017-18.280, p < 0.0001). CONCLUSION: QRS prolongation occurs in a significant proportion of patients with LVD and portends adverse outcome. Advanced age, prolonged QRS and larger left atria are potential predictors. Routine monitoring is justified and physicians may choose to plan ahead for resynchronization therapy in patients at risk for QRS prolongation.

Late in-hospital pressure gradient measurements improve prediction of long-term outcome of alcohol septal ablation in hypertrophic cardiomyopathy.

BACKGROUND: Left ventricular outflow gradient is associated with increased morbidity and mortality in hypertrophic cardiomyopathy. Alcohol septal ablation is the alternative to surgery in cases refractory to drug therapy. The implication of LVOG measured 1 week post-ASA for prediction of outcome is unknown. OBJECTIVE: To observe the pattern of LVOG course and prediction of long-term clinical and hemodynamic outcome of ASA. METHODS: Baseline clinical and echocardiographic parameters were prospectively recorded in 14 consecutive patients with a first ASA, at the time of ASA, 3 and 7 days after ASA (in-hospital), and 3 and > or = 12 months after ASA (last follow-up). RESULTS: There was improvement in NYHA class, exercise parameters and LVOG in 11 of 14 patients (P < 0.005 in all). Maximal creatine kinase level was lower than 500 U/L in those without such improvement and 850 U/L or higher in successful cases. LVOG dropped from 79 +/- 30 to 19 +/- 6 mmHg after the ASA. LVOG was 50 +/- 21 mmHg on day 3, 39 +/- 26 on day 7, 32 +/- 26 at 3 months and 24 +/- 20 mmHg at last follow-up. LVOG identified 27% sustained procedural successes on day 3 and 73% on day 7. The overall predictive accuracy of the test for sustained success and failure was 36% on day 3 and 71% on day 7. Combination of maximal CK and LVOG on day 7 showed four distinct outcome patterns: "early success" with low LVOG and high CK (73% of successful cases), "late success" with high LVOG and high CK, and "early failure" and "late failure" with both low CK and high or low LVOG, respectively. CONCLUSION: LVOG measurement 7 days post-ASA combined with maximal CK levels predicts late procedural outcome in the majority of patients.

Brain natriuretic peptide and the risk of ventricular tachyarrhythmias in mildly symptomatic heart failure patients enrolled in MADIT-CRT.

BACKGROUND: There are limited data about the correlation between brain natriuretic peptide (BNP) levels and arrhythmic risk assessment in patients who receive device therapy for the treatment of heart failure (HF) or for the prevention of sudden cardiac death. OBJECTIVES: We aimed to investigate the association between BNP levels and the risk of ventricular tachyarrhythmias among mildly symptomatic HF patients who receive an intracardiac defibrillator (ICD) with or without cardiac resynchronization therapy (respectively, CRT-D or CRT). METHODS: The study population involved 1197 patients enrolled in MADIT-CRT. Plasma BNP was measured in a core laboratory at baseline and after 1-year follow-up. Ventricular tachycardia/fibrillation (VT/VF) events were identified from ICD/CRT-D interrogations. RESULTS: Multivariate Cox hazards regression modeling showed that elevated baseline (> median = 72 ng/L) and 1-year BNP were associated with a significant increase in the risk of VT/VF (HR = 1.36, P = .026; and HR = 1.79, P < .001, respectively); and VT/VF or death (HR = 1.37, P = .008; and HR = 1.84, P < .0001, respectively) during follow-up. At 1 year post device implantation, BNP levels were significantly lower among study patients treated with CRT-D as compared with those who received ICD only (P = .014). CRT-D patients who had greater than median reductions in BNP levels (greater than one-third reduction of initial value) experienced a significantly lower risk of subsequent VT/VF (HR = 0.61, P = .021) and VT/VF or death (HR = 0.45, P < .0001) as compared to patients without such reductions. CONCLUSIONS: In MADIT-CRT, elevated baseline and follow-up BNP levels were independent predictors of increased risk for subsequent ventricular tachyarrhythmias, whereas BNP reductions following CRT-D implantation identified patients with a lower incidence of VT/VF during follow-up.

Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel.

BACKGROUND: The hereditary long-QT syndrome is characterized by prolonged ventricular repolarization and a variable clinical course with arrhythmia-related syncope and sudden death. Mutations involving the human ether-a-go-go-related gene (HERG) channel are responsible for the LQT2 form of long-QT syndrome, and in cellular expression studies these mutations are associated with reduction in the rapid component of the delayed rectifier repolarizing current (I(Kr)). We investigated the clinical features and prognostic implications of mutations involving pore and nonpore regions of the HERG channel in the LQT2 form of this disorder. METHODS AND RESULTS: A total of 44 different HERG mutations were identified in 201 subjects, with 14 mutations located in the pore region (amino acid residues 550 through 650). Thirty-five subjects had mutations in the pore region and 166 in nonpore regions. Follow-up extended through age 40 years. Subjects with pore mutations had more severe clinical manifestations of the genetic disorder and experienced a higher frequency (74% versus 35%; P<0.001) of arrhythmia-related cardiac events occurring at earlier age than did subjects with nonpore mutations. Multivariate Cox proportional hazard regression analysis revealed that pore mutations dominated the risk, with hazard ratios in the range of 11 (P<0.0001) for QTc at 500 ms, with a 16% increase in the pore hazard ratio for each 10-ms increase in QTc. CONCLUSION: Patients with mutations in the pore region of the HERG gene are at markedly increased risk for arrhythmia-related cardiac events compared with patients with nonpore mutations.

Modulating effects of age and gender on the clinical course of long QT syndrome by genotype.

OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children < or = 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS; Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.

Ethnic differences among implantable cardioverter defibrillators recipients in Israel.

Heart failure is an increasingly common condition arising from a variety of different pathophysiological processes. Little is known about the unique features of Israeli Arabs who present with heart failure and who undergo cardiac device implantation. The study population comprised of 4,671 patients who were enrolled in the national Israeli Implantable Cardioverter Defibrillator registry. We compared demographic, clinical, and echocardiographic characteristics; device-related indications; and outcomes between Israeli Arabs (n = 733) and Jews (n = 3,938), who were enrolled in the registry from July 2010 through December 2013. Israeli Arabs constituted 15.7% of the study population. They were younger at presentation compared with Jews (57 ± 15 vs 66 ± 12 years, respectively; p <0.001), with a greater burden of co-morbidities, including diabetes mellitus and chronic obstructive lung disease and smoking. In addition, Arab patients had a greater frequency of non-ischemic cardiomyopathy (40.2% vs 24.6%, respectively; p <0.001), which was associated with a greater frequency of familial history of sudden cardiac death. During 15 ± 9 month follow-up, the mortality rates and appropriate device therapy were similar in both ethnic groups. In conclusion, Israeli Arab patients implanted with implantable cardioverter defibrillators display unique clinical features with greater prevalence of non-ischemic cardiomyopathy characterized by an early-onset and rapid deterioration.

Cryo-Balloon Ablation of the Right Superior Pulmonary Vein Involving the Anterior Right Ganglionated Plexus for Speech and Breathing Induced Atrial Tachycardia.

Targeting ganglionated plexi (GP) during catheter ablation of atrial fibrillation (AF) is associated with improved outcome. We present a patient with speech and breathing induced atrial tachycardia (AT) originating in the superior vena cava (SVC) and the right superior pulmonary vein (RSPV), near the anatomical location of the anterior right GP (ARGP). The trigger for the arrhythmia appeared to be vagal discharge from the GP, possibly induced by local stretch. Ablation with a 28 mm cryo-balloon advanced to the RSPV orifice through a patent foramen ovale (PFO) abolished the arrhythmia, probably involving the underlying parasympathetic influx to the SVC and RSPV myocardial sleeves.

Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study.

OBJECTIVES: This study sought to evaluate the safety of the Coronary Sinus Reducer (Neovasc Medical, Inc., Or Yehuda, Israel) as a potential alternate therapy for patients with refractory angina who are not candidates for conventional revascularization procedures. BACKGROUND: Increased coronary sinus (CS) pressure can reduce myocardial ischemia by redistribution of blood from nonischemic to ischemic territories. The Coronary Sinus Reducer is a percutaneous implantable device designed to establish CS narrowing and to elevate CS pressure. In preclinical experiments, implantation of the Reducer was safe and was associated with improved ischemic parameters. In the present study, the safety and feasibility of the Coronary Sinus Reducer was evaluated in patients with refractory angina who were not candidates for revascularization. METHODS: Fifteen coronary artery disease patients with severe angina and reversible ischemia were electively treated with the Reducer. Clinical evaluation, dobutamine echocardiography, thallium single-photon emission computed tomography, and administration of an angina questionnaire were performed before and 6 months after implantation. Cardiac computed tomography was performed 2 days and 6 months after implantation. RESULTS: All procedures were completed successfully. No procedure-related adverse events occurred during the periprocedural and the follow-up periods. Angina score improved in 12 of 14 patients. Average Canadian Cardiovascular Society score was 3.07 at baseline and 1.64 at follow-up (n = 14, p < 0.0001). Stress-induced ST-segment depression was reduced in 6 of 9 patients and was eliminated in 2 of these 6 (p = 0.047). The extent and severity of myocardial ischemia by dobutamine echocardiography and by thallium single-photon emission computed tomography was reduced (p = 0.004 [n = 13] and p = 0.042 [n = 10], respectively). CONCLUSIONS: Implantation of the Coronary Sinus Reducer is feasible and safe. These findings, along with the clinical improvement observed, support further evaluation of the Reducer as an alternative treatment for patients with chronic refractory angina who are not candidates for coronary revascularization.

Glycoprotein IIb/IIIa receptor antagonists in acute myocardial infarction and primary coronary stenting: Not always effective.

Glycoprotein IIb/IIIa antagonists have been shown to be effective in reducing thrombotic complications prior to high-risk coronary interventions. Some studies have reported improved coronary flow after abciximab in slow or no-reflow phenomenon. We report a case in which abciximab did not clear the thrombotic occlusion or restore artery flow. Further studies are needed into the refractory no-flow phenomenon.