Do all intra-ventricular conduction defect ECG patterns respond equally to CRT?

PURPOSE: Response to cardiac resynchronization therapy (CRT) is well-established in patients with typical left bundle branch block (LBBB) but modest or even negative in those with intraventricular conduction delay (IVCD). However, IVCD pattern is heterogeneous, and it is possible that QRS patterns may also respond to CRT. METHODS: Consecutive baseline ECGs of 239 patients implanted between 2007 and 2010 with CRT were analyzed. ECGs were classified into the following three groups: (a) typical LBBB (TLBBB) according to accepted guidelines (n = 67); (b) IVCD with LBBB pattern criteria in V1, 1, and aVL but with QS or rS in V5-V6 which we defined as atypical LBBB (ALBBB) (n = 74); and (c) all other IVCD (OIVCD) patterns (n = 98). Endpoints were 2 years mortality and echocardiographic response, defined as a decrease of ≥ 10% in indexed LVESV or an increase of ≥ 5% in left ventricular ejection fraction at 1 year of follow-up. RESULTS: Baseline clinical characteristics were similar among all the three groups. Rates of echocardiographic response were lower among those with OIVCD compared to those with LBBB and ALBBB (50% vs. 75% and 72%, respectively, p = 0.01 for both comparisons). A multivariable model showed a lower likelihood of echocardiographic response in OIVCD [HR = 0.40; (0.16-0.98)] and a similar likelihood in ALBBBB [HR = 0.98; (0.40-2.40)] compared to TLBBB. Cumulative 2-year survival was 88% in ALBBB, 86% in TLBBB, and 76% in OIVCD (p value = 0.011). CONCLUSION: Patients with ALBBB may have a favorable echocardiographic response to CRT and display similar survival rates to typical LBBB. This subgroup of IVCD should be considered for CRT. Atypical left bundle branch morphology defined as QS or rS in lead V1, broad R waves in lead I, and aVL but with QS or rS in V5-V6 is associated with favorable echocardiographic response to CRT and displays similar survival rates to typical LBBB patients.

Sildenafil for Pulmonary Hypertension in the Early Postoperative Period After Mitral Valve Surgery.

OBJECTIVES: The phosphodiesterase-5 inhibitor sildenafil was developed for the treatment of pulmonary hypertension. The authors investigated the efficacy and safety of sildenafil in the early postoperative period after mitral valve surgery in patients with pulmonary hypertension. DESIGN: A double-blind, placebo-controlled randomized trial was performed. SETTING: The trial was performed in a single tertiary referral center. PARTICIPANTS: Fifty consecutive patients who experienced pulmonary hypertension and underwent mitral valve surgery. INTERVENTIONS: Patients were randomly assigned to the following 2 groups: 25 patients received 20 mg sildenafil every 8 hours, and the remaining 25 patients received placebo during the same period. Hemodynamic parameters were studied by using a pulmonary artery catheter at baseline and every 6 hours up to 36 hours. RESULTS: Patients who received sildenafil showed a decrease in mean pulmonary pressure, from 32 ± 7 mmHg at baseline to 26 ± 3 mmHg after 36 hours, whereas no change was seen in patients who received placebo (mean pulmonary pressure 34 ± 6 mmHg at baseline and 35 ± 5 mmHg after 36 h) (p < 0.001). No significant changes in systemic hemodynamic and oxygenation were observed. Patients who received sildenafil compared with those who received placebo had a median mechanical lung ventilation time of 16 (10-31) hours versus 19 (13-41) hours (p = 0.431), intensive care unit stay of 74 (44-106) hours versus 91 (66-141) hours (p = 0.410), and a total hospitalization stay of 7 (5-10) days versus 11 (7-15) days (p = 0.009). CONCLUSIONS: The immediate postoperative administration of sildenafil after mitral valve surgery is safe. Sildenafil demonstrates a favorable decreasing effect on pulmonary vascular pressure without systemic hypotension and ventilation-perfusion mismatch.

An innovative appendage invagination procedure to reduce thrombus formation - a numerical model.

Invagination is an innovative technique for closing the left atrial appendage (LAA) to reduce the risk of thrombi formation. The influence of LAA invagination on the flow fields in the atria was investigated based on a computational fluid dynamics. The simulation results demonstrated that the novel invagination process can eliminate low velocities (blood stasis) and low shear rate and thus decrease the risk of thrombus formation during atrial fibrillation. This innovative technique may enhance the clinical treatment of patients with atrial fibrillation by improving the atrial flow field while lowering the risk of creating emboli.

Effect of supplemented intake of omega-3 fatty acids on arrhythmias in patients with ICD: fish oil therapy may reduce ventricular arrhythmia.

PURPOSE: The aim of this study was to evaluate the effects of fish oils, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on ventricular tachyarrhythmic episodes (VTEs) in implantable cardioverter defibrillator (ICD) recipients with ischemic cardiomyopathy. METHODS: One hundred five ICD recipients with ischemic cardiomyopathy received 3.6 g of EPA and DHA and placebo for 6 months, each at a random order, with a 4-month washout period between treatments. Eighty-seven patients completed the 16-month study protocol. The primary end point was any VTE (including sustained and non-sustained ventricular tachycardias at a rate of >150 bpm) as recorded by the ICDs. Secondary end points included device therapy (anti-tachycardia pacing (ATP) or shocks). RESULTS: During treatment with fish oils, there was a significant increase in EPA and DHA concentrations in red blood cells (RBCs) and subcutaneous fat tissue. Among 87 patients who completed the study protocol, the mean number of VTEs was significantly lower during treatment with fish oil (1.7) vs. placebo (5.6; p = 0.035). Appropriate device therapy for VTE occurred in 18 (21%) patients. Fish oil therapy was associated with a trend toward fewer VTEs terminated with ATP (2.8 ± 13.7 vs. 0.5 ± 2.1, respectively; p = 0.077). VTE terminated by ICD shocks, however, was rare, and rates were similar between both groups (0.11 ± 0.6 vs. 0.10 ± 0.4, p = not significant, respectively). CONCLUSIONS: Our data suggest that fish oil therapy may be associated with a reduction in the frequency of VTE in ICD recipients with ischemic cardiomyopathy.

Triggers and Timing of Acute Coronary Syndromes.

Previous studies have shown that an acute coronary syndrome (ACS) may be triggered by external activities; however, their frequency, predictors, and significance are uncertain. We evaluated data from the National Israel Survey of Acute Coronary Syndromes, which was conducted in 2004 (February to March) in all 25 coronary care units and cardiac wards in Israel. Demographic and clinical data were recorded for consecutive participants, including potential triggers and time of symptom onset of ACS. Among the 1,849 patients who completed the trigger question, 1/4 (25.9%) reported a possible trigger, comprising heavy physical exertion (15.2%), emotional stress (8.3%), anger (1.1%), heavy meal (1.3%), and sexual activity (0.5%). Predictors of a triggered ACS were age <65 years, previous angina, no previous angiotensin-converting enzyme inhibitors/angiotensin 2 receptor blockers, impaired functional class, not having typical chest pain on admission, and a final diagnosis of unstable angina. The highest proportion of triggered ACS was between noon and 6 p.m. Physical exertion as a trigger was associated with reduced in-hospital mortality (0.4% vs 2.8%, p <0.05) and 1-year mortality. Emotional stress as a trigger did not influence in-hospital or 1-year mortality; however among those discharged from hospital, it was associated with increased 30-day rehospitalization (27.6% vs 19.3%, p <0.05) and a trend toward increased mortality (4.1% vs 2.0%, p = 0.10).

Viral delivered gene therapy to treat catecholaminergic polymorphic ventricular tachycardia (CPVT2) in mouse models.

BACKGROUND: The recessive form of catecholaminergic polymorphic ventricular tachycardia 2 (CPVT2) is caused by mutations in cardiac calsequestrin (CASQ2), leading to protein deficiency. OBJECTIVES: The aims of this study were to develop a viral-delivered gene therapy for CPVT2 and to determine the relationship between CASQ2 expression and antiarrhythmic efficacy in a murine model. METHODS: We used a murine model of CPVT2 caused by the D307H human mutation (CASQ2D307H) or CASQ2 knockout (CASQ2Δ/Δ). Adeno-associated virus (AAV) particles containing the CASQ2 gene (AAVCASQ2) were injected into the heart or intraperitoneally to 12-week-old mice. A telemetry device was implanted, and mice underwent provocation testing 7-8 weeks after gene therapy. RESULTS: CASQ2Δ/Δ mice injected intracardiacally with AAVCASQ2 expressed 40% ± 25% of the normal CASQ2 protein level, which was increased compared to untreated CASQ2Δ/Δ mice (n = 10; P < .05). Intraperitoneal therapy led to a significantly elevated expression of the CASQ2 protein, which was comparable in CASQ2D307H (n = 12) and CASQ2Δ/Δ (n = 4) mice. All control mice with CPVT2 had nonsustained ventricular tachycardia (VT) and 8 of 13 had sustained VT on provocation. Expressing ≥33% of the normal CASQ2 level was needed to protect from nonsustained VT as well as stress-induced premature ventricular contractions. Lower levels of expression prevented sustained VT in AAVCASQ2-treated mice (0 of 26; P < .001 vs controls). CONCLUSION: AAVCASQ2 displays a long-lasting capacity to attenuate and potentially cure CPVT2. Systemic delivery is feasible and convenient, reproducibly providing adequate levels of transgene expression. Antiarrhythmic efficacy depends on the CASQ2 level: ≥33% of the normal CASQ2 level is needed to prevent arrhythmia. However, even lower levels of protein protect from sustained VT, thereby potentially reducing the risk of sudden death.

SK4 K+ channels are therapeutic targets for the treatment of cardiac arrhythmias.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-provoked ventricular arrhythmia, which also manifests sinoatrial node (SAN) dysfunction. We recently showed that SK4 calcium-activated potassium channels are important for automaticity of cardiomyocytes derived from human embryonic stem cells. Here SK4 channels were identified in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from healthy and CPVT2 patients bearing a mutation in calsequestrin 2 (CASQ2-D307H) and in SAN cells from WT and CASQ2-D307H knock-in (KI) mice. TRAM-34, a selective blocker of SK4 channels, prominently reduced delayed afterdepolarizations and arrhythmic Ca2+ transients observed following application of the ß-adrenergic agonist isoproterenol in CPVT2-derived hiPSC-CMs and in SAN cells from KI mice. Strikingly, in vivo ECG recording showed that intraperitoneal injection of the SK4 channel blockers, TRAM-34 or clotrimazole, greatly reduced the arrhythmic features of CASQ2-D307H KI and CASQ2 knockout mice at rest and following exercise. This work demonstrates the critical role of SK4 Ca2+-activated K+ channels in adult pacemaker function, making them promising therapeutic targets for the treatment of cardiac ventricular arrhythmias such as CPVT.

Tricuspid Regurgitation following Lead Extraction: Risk Factors and Clinical Course.

BACKGROUND: Transvenous lead extraction can lead to tricuspid valve damage. OBJECTIVES: To assess the incidence, risk factors and clinical outcome of tricuspid regurgitation (TR) following lead extraction. METHODS: We prospectively collected data on patients who underwent lead extraction at the Sheba Medical Center prior to laser use (i.e., before 2012). Echocardiography results before and following the procedure were used to confirm TR worsening, defined as an echocardiographic increase of at least one TR grade. Various clinical and echocardiographic parameters were analyzed as risk factors for TR. Clinical and echocardiographic follow-up was conducted to assess the clinical significance outcome of extraction-induced TR. RESULTS: Of 152 patients who underwent lead extraction without laser before 2012, 86 (56%) (192 electrodes) had echocardiography results before and within one week following the procedure. New or worsening TR was discovered in 13 patients (15%). Use of mechanical tools and younger age at extraction were found on multivariate analysis to be factors for TR development (P = 0.04 and P = 0.03 respectively). Average follow-up was 22.25 ± 21.34 months (range 8-93). There were no significant differences in the incidence of right-sided heart failure (50% vs. 23%, P = 0.192) or hospitalizations due to heart failure exacerbations (37.5% vs. 11%, P = 0.110). No patient required tricuspid valve repair or replacement. Death rates were similar in the TR and non-TR groups (20% vs. 33%). CONCLUSIONS: TR following lead extraction is not uncommon but does not seem to affect survival or outcomes such as need for valve surgery. Its long-term effects remain to be determined.

Peripheral microcirculatory hemodynamic changes in patients with myocardial ischemia.

BACKGROUND: Patients with coronary heart disease demonstrate changes in skin microcirculation and a decrease in cutaneous blood mass. OBJECTIVE: The goal of this study was to assess the feasibility of diagnosing myocardial ischemia based on peripheral microcirculatory variables. METHODS: The skin microcirculatory measurements were monitored using an LPT system comprising a Laser Doppler Flowmeter (LDF), a photoplethysmograph (PPG) and a transcutaneous oxygen tension device (tc-PO2). Concurrently, heart rate and blood pressure were monitored. Measurements were performed before and after exercise stress test. Subjects were divided into ischemic (20) and nonischemic (27) patients based on myocardial perfusion imaging (MPI). RESULTS: The results indicate differences in LPT variables between ischemic and nonischemic patients following exercise, while no differences in the central variable values were observed between the two groups. CONCLUSIONS: Peripheral microcirculatory variables may be useful for non-invasive assessment of myocardial ischemia. The system has clinical potential for sensitive and noninvasive monitoring of vital variables during medical procedures in clinics, as well as in home care for patients who suffer from ischemic cardiac diseases.

Functional abnormalities in iPSC-derived cardiomyocytes generated from CPVT1 and CPVT2 patients carrying ryanodine or calsequestrin mutations.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by syncope and sudden death occurring during exercise or acute emotion. CPVT is caused by abnormal intracellular Ca(2+) handling resulting from mutations in the RyR2 or CASQ2 genes. Because CASQ2 and RyR2 are involved in different aspects of the excitation-contraction coupling process, we hypothesized that these mutations are associated with different functional and intracellular Ca(²+) abnormalities. To test the hypothesis we generated induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CM) from CPVT1 and CPVT2 patients carrying the RyR2(R420Q) and CASQ2(D307H) mutations, respectively, and investigated in CPVT1 and CPVT2 iPSC-CM (compared to control): (i) The ultrastructural features; (ii) the effects of isoproterenol, caffeine and ryanodine on the [Ca(2+) ]i transient characteristics. Our major findings were: (i) Ultrastructurally, CASQ2 and RyR2 mutated cardiomyocytes were less developed than control cardiomyocytes. (ii) While in control iPSC-CM isoproterenol caused positive inotropic and lusitropic effects, in the mutated cardiomyocytes isoproterenol was either ineffective, caused arrhythmias, or markedly increased diastolic [Ca(2+) ]i . Importantly, positive inotropic and lusitropic effects were not induced in mutated cardiomyocytes. (iii) The effects of caffeine and ryanodine in mutated cardiomyocytes differed from control cardiomyocytes. Our results show that iPSC-CM are useful for investigating the similarities/differences in the pathophysiological consequences of RyR2 versus CASQ2 mutations underlying CPVT1 and CPVT2 syndromes.

Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder causing life-threatening arrhythmias whenever sympathetic activity increases. ß-Βlockers are the mainstay of therapy; when they fail, implantable cardioverter-defibrillators (ICDs) are used but often cause multiple shocks. Preliminary results with flecainide appear encouraging. We proposed left cardiac sympathetic denervation (LCSD) as useful additional therapy, but evidence remains anecdotal. METHODS AND RESULTS: We report 63 patients with CPVT who underwent LCSD as secondary (n=54) or primary (n=9) prevention. The median post-LCSD follow-up was 37 months. The 9 asymptomatic patients remained free of major cardiac events. Of the 54 patients with prior major cardiac events either on (n=38) or off (n=16) optimal medical therapy, 13 (24%) had at least 1 recurrence: 0 patients had an aborted cardiac arrest, 2 patients had syncope only, 10 patients had ≥1 appropriate ICD discharges, and 1 patient died suddenly. The 1- and 2-year cumulative event-free survival rates were 87% and 81%. The percentage of patients with major cardiac events despite optimal medical therapy (n=38) was reduced from 100% to 32% (P<0.001) after LCSD, and among 29 patients with a presurgical ICD, the rate of shocks dropped by 93% from 3.6 to 0.6 shocks per person per year (P<0.001). Patients with an incomplete LCSD (n=7) were more likely to experience major cardiac events after LCSD (71% versus 17%; P<0.01) than those with a complete LCSD. CONCLUSIONS: LCSD is an effective antifibrillatory intervention for patients with CPVT. Whenever syncope occurs despite optimal medical therapy, LCSD could be considered the next step rather than an ICD and could complement ICDs in patients with recurrent shocks.

Noninvasive monitoring of peripheral microcirculatory hemodynamics under varying degrees of hypoxia.

The effect of hypoxia on skin blood flow was examined in anesthetized rabbits during induction of various levels of hypoxia. Peripheral perfusion and oxygenation were monitoring using a combined system (LPT) composed of a laser Doppler flowmeter (LDF), a photoplatysmograph (PPG), and a transcutaneous oxygen tension monitor (tc-PO2). Central blood parameters (PaO2, HCO3(-), SaO2, pH, and lactate) were measured concomitantly throughout the experiment. A continuous decline was found in both peripheral and central values, depending on the severity of the hypoxia. The results clearly indicate that monitoring peripheral indices with the LPT system enables monitoring changes of vital blood parameters during hypoxia. The system has clinical potential for sensitive and noninvasive monitoring of vital variables during medical procedures in clinics, as well as for homecare for patients with respiratory diseases. Minimizing the system may be useful in various conditions of exposure to low oxygen levels, such as during mountain climbing.

Clinical outcomes and cost effectiveness of accelerated diagnostic protocol in a chest pain center compared with routine care of patients with chest pain.

AIMS: The aim of this study was to compare in patients presenting with acute chest pain the clinical outcomes and cost-effectiveness of an accelerated diagnostic protocol utilizing contemporary technology in a chest pain unit versus routine care in an internal medicine department. METHODS AND RESULTS: Hospital and 90-day course were prospectively studied in 585 consecutive low-moderate risk acute chest pain patients, of whom 304 were investigated in a designated chest pain center using a pre-specified accelerated diagnostic protocol, while 281 underwent routine care in an internal medicine ward. Hospitalization was longer in the routine care compared with the accelerated diagnostic protocol group (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients (98%) vs. 57 (20%) routine care patients underwent non-invasive testing, (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients in both groups had non-invasive imaging testing. Accelerated diagnostic protocol patients compared with those receiving routine care was associated with a lower incidence of readmissions for chest pain [8 (3%) vs. 24 (9%), p<0.01], and acute coronary syndromes [1 (0.3%) vs. 9 (3.2%), p<0.01], during the follow-up period. The accelerated diagnostic protocol remained a predictor of lower acute coronary syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95% 0.14-0.59)]. Cost per patient was similar in both groups [($2510 vs. $2703 for the accelerated diagnostic protocol and routine care group, respectively, (p = 0.9)]. CONCLUSION: An accelerated diagnostic protocol is clinically superior and as cost effective as routine in acute chest pain patients, and may save time and resources.

Functional response to cardiac resynchronization therapy in patients with renal dysfunction and subsequent long-term mortality.

INTRODUCTION: Renal dysfunction is associated with increased morbi-mortality in heart failure patients. Data regarding functional and clinical efficacy of cardiac resynchronization therapy (CRT) in this population are limited. METHODS AND RESULTS: We aimed to evaluate the rate of functional response to CRT in patients with renal dysfunction and its association with long-term mortality. Our study included a total of 179 consecutive patients implanted between 2007 and 2010. The rate of functional response to CRT (defined by a composite score using New York Heart Association functional class, 6-minute walk test, and quality of life) was compared between patients with and without renal dysfunction (defined as eGFR < or ≥60 mL/min/1.73 m(2) ). Survival analysis estimates were constructed according to the Kaplan-Meier method, with results comparison using the log-rank test. During a median follow-up of 4.2 years, 73 patients (40%) died. Patients with low eGFR were older (72 ± 8 years vs. 64 ± 12 years; P < 0.001), and had higher prevalence of ischemic heart disease (75% vs. 53%; P = 0.003). Functional response rates did not differ significantly between patients with and without renal dysfunction (58% and 69%, respectively; P = 0.14). Despite overall higher mortality in patients with low eGFR (53.8% vs. 22.7%; P < 0.001), the presence of functional response at 1 year among patients with renal dysfunction was still independently associated with an improved long-term survival (HR = 0.49 [95%CI: 0.28-0.83]; P = 0.009). CONCLUSION: Functional response to CRT at 1 year does not differ significantly between patients with or without kidney disease, and is an independent predictor of improved long-term survival in patients with renal dysfunction.

Alpha blockade potentiates CPVT therapy in calsequestrin-mutant mice.

BACKGROUND: Spontaneous calcium release evoking delayed afterdepolarization is believed to cause catecholaminergic polymorphic ventricular tachycardia (CPVT), a lethal human arrhythmia provoked by exercise or emotional stress. ß-Adrenergic blockers are the drug of choice, but fail to achieve complete arrhythmia control in some patients. These individuals often require flecainide, device implantation, and/or sympathetic denervation. OBJECTIVE: To optimize the arrhythmia therapy by pharmacological inhibition of the sympathetic nervous system in the homozygous calsequestrin knockout (CASQ2(Δ/Δ)) mouse model of CPVT2. METHODS: A heart telemetry device was implanted for continuous electrocardiographic recording at rest and during provocation testing. Calcium transients and abnormal calcium release were studied in cardiomyocytes isolated from adult mice. Adrenergic receptor expression was determined by using Western blotting and confocal microscopy. RESULTS: Adult CASQ2(Δ/Δ) mice suffer from complex ventricular arrhythmia at rest and ventricular tachycardia during treadmill exercise and after epinephrine injection. ß-Adrenergic blockers, propranolol and metoprolol, attenuated arrhythmia at rest but not after stress. Reserpine had no efficacy in controlling arrhythmia. Agents with α-blocking activity, phentolamine or labetalol, abolished both exercise- and epinephrine-induced arrhythmia. In contrast, injection of α-adrenergic agonist phenylephrine reproducibly provoked ventricular tachycardia. Isolated cardiomyocytes from CASQ2(Δ/Δ) mice had delayed calcium release waves upon exposure to sympathetic agonists, which were abolished by phentolamine. Hearts of calsequestrin-mutant mice expressed more α1-adrenergic receptor than did wild type control mice (P < .05). CONCLUSION: We identified a contribution of the α-adrenergic pathway to the pathogenesis of catecholamine-induced arrhythmia. α-Blockade emerges as an effective therapy in the murine model of CPVT2 and should be tried in humans resistant to ß-blockers.

Safety and efficacy of strategic implantable cardioverter-defibrillator programming to reduce the shock delivery burden in a primary prevention patient population.

AIMS: Strategically chosen ventricular tachycardia (VT)/ventricular fibrillation (VF) detection and therapy parameters aimed at reducing shock deliveries were proven effective in studies that utilized single manufacturer devices with a follow-up of up to 1 year. Whether these beneficiary effects can be generalized to additional manufacturers and be maintained for longer periods is to be determined. Our aim was to evaluate the durability and applicability of the programming of strategic implantable cardioverter-defibrillators (ICDs) of various manufacturers, which is aimed at reducing the shock delivery burden in primary prevention ICD recipients. METHODS AND RESULTS: A retrospective analysis of prospectively collected data of 300 ICD recipients of various manufacturers was conducted; 160 devices were strategically programmed to reduce shocks and 140 were not. The primary endpoint was the composite of death and appropriate shocks. Additional outcomes were inappropriate shocks, syncope events, and non-sustained VTs. At a median follow-up of 24 months, 19 patients died, 31 received appropriate shocks, and 41 received inappropriate shocks. Multivariate analysis showed that strategic programming dedicated to shock reduction was associated with a 64% risk reduction in the primary endpoint [hazard ratio (HR): 0.13-0.93; P = 0.03] and a 70% reduction in inappropriate shock deliveries (HR: 0.16-0.72; P = 0.01). Very few syncope events occurred (five patients, 1.6%), and there was no between-group difference in this outcome. CONCLUSION: Utilization of strategically chosen VT/VF detection and therapy parameters was found to be effective and safe in ICDs of various manufacturers at a median follow-up period of 2 years among primary prevention patients.

Morphological features of the P-waves at surface electrocardiogram as surrogate to mechanical function of the left atrium following a successful modified maze procedure.

AIMS: Absent left atrium (LA) mechanical contraction may occur following the modified Cox-maze operation, and was found to impose a potential risk for the occurrence of thrombo-embolic stroke. It is unknown whether certain morphological P-wave characteristics can surrogate absent LA mechanical activity. The aim of this study was to evaluate the morphological features of the P-waves on the surface electrocardiogram (ECG) of patients who underwent the maze operation and to relate them to the contractile profile of the LA. METHODS AND RESULTS: Electrocardiogram tracings of 150 consecutive patients that were in sustained sinus rhythm following the maze operation were evaluated. P-waves were scrutinized for morphology, duration, axis, and amplitude. Clinical, surgery-related, and echocardiographic data were collected and analysed. Forty-seven patients (31%) had no evidence of LA contraction at 3 months after surgery (baseline assessment) and on follow-up echocardiography. Multivariate analysis showed that a positive-only P-wave deflection at lead V1 (P = 0.03), a negative-only deflection at aVL, and a P-wave amplitude of ≤ 0.05 mV at the septal-anterior leads (P < 0.001 for both) were associated with absent LA mechanical contraction. In a secondary analysis, a risk score involving the above three parameters was developed for the prediction of stroke occurrence. Patients at the high-risk score group had a 30% survival freedom of stroke compared with 70% for patients at intermediate risk (P < 0.001). CONCLUSION: Absent LA mechanical contraction following the modified maze operation may be accompanied by a distinguished pattern of the P-waves on the surface ECG.

The role of mutant protein level in autosomal recessive catecholamine dependent polymorphic ventricular tachycardia (CPVT2).

Humans and genetically engineered mice with recessively inherited CPVT develop arrhythmia which may arise due to malfunction or degradation of calsequestrin (CASQ2). We investigated the relation between protein level and arrhythmia severity in CASQ2(D307H/D307H) (D307H), compared to CASQ2(Δ/Δ) (KO) and wild type (WT) mice. CASQ2 expression and Ca²âº transients were recorded in cardiomyocytes from neonatal or adult mice. Arrhythmia was studied in vivo using heart rhythm telemetry at rest, exercise and after epinephrine injection. CASQ2 protein was absent in KO heart. Neonatal D307H and WT hearts expressed significantly less CASQ2 protein than the level found in the adult WT. Adult D307H expressed only 20% of CASQ2 protein found in WT. Spontaneous Ca²âº release was more prevalent in neonatal KO cardiomyocytes (89%) compared to 33-36% of either WT or D307H, respectively, p<0.001. Adult cardiomyocytes from both mutant mice had more Ca²âº abnormalities compared to control (KO: 82%, D307H 63%, WT 12%, p<0.01). Calcium oscillations were most common in KO cardiomyocytes. We then treated mice with bortezomib to inhibit CASQ2(D307H) degradation. Bortezomib increased CASQ2 expression in D307H hearts by ∼50% (p<0.05). Bortezomib-treated D307H mice had lower CPVT prevalence and less premature ventricular beats during peak exercise. No benefit against arrhythmia was observed in bortezomib treated KO mice. These results indicate that the mutant CASQ2(D307H) protein retains some of its physiological function. Its expression decreases with age and is inversely related to arrhythmia severity. Preventing the degradation of mutant protein should be explored as a possible therapeutic strategy in appropriate CPVT2 patients.

Dobutamine stress MRI for the assessment of coronary artery disease: initial clinical experience in Israel.

BACKGROUND: Over the past few years dobutamine stress magnetic resonance (DSMR) has proven its efficacy as an integral part of the diagnosis of coronary artery disease (CAD). OBJECTIVES: To present the feasibility and safety of DSMR in Israel. METHODS: Thirty patients with suspected or known CAD were studied. DSMR images were acquired during short breath-holds in three short axis views and four-, two-, and three-chamber views. Patients were examined at rest and during a standard dobutamine-atropine protocol. Regional wall motion was assessed in a 16-segment model and the image quality was evaluated using a four-point scale for the visibility of the endocardial border. RESULTS: In 28 patients (93.4%) DSMR was successfully performed and completed within an average of 55 +/- 6 minutes. One patient could not be examined because of claustrophobia and another patient, who was on beta-blockers, did not reach the target heart rate. Image quality was excellent and there was no difference between the rest and stress images in short axis (3.91 +/- 0.29 vs. 3.88 +/- 0.34, P = 0.13, respectively) and long axis (3.83 +/- 0.38 vs. 3.70 +/- 0.49, P = 0.09, respectively) views. Segmental intra-observer agreement for wall motion contractility at rest and stress cine images was almost perfect (K = 0.88, 95% confidence interval = 0.93-0.84, and K = 0.82, 95% CI = 0.88-0.76) respectively. No serious side effects were observed during DSMR. CONCLUSION: The present study confirms the feasibility, safety and excellent image quality of DSMR for the diagnosis of coronary artery diseases.