A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.

Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.

In vivo pulsed-field ablation in healthy vs. chronically infarcted ventricular myocardium: biophysical and histologic characterization.

AIMS: Data on ventricular pulsed-field ablation (PFA) are sparse in the setting of chronic myocardial infarction (MI). The objective of this study was to compare the biophysical and histopathologic characteristics of PFA in healthy and MI swine ventricular myocardium. METHODS AND RESULTS: Myocardial infarction swine (n = 8) underwent coronary balloon occlusion and survived for 30 days. We then performed endocardial unipolar, biphasic PFA of the MI border zone and a dense scar with electroanatomic mapping and using an irrigated contact force (CF)-sensing catheter with the CENTAURI System (Galaxy Medical). Lesion and biophysical characteristics were compared with three controls: MI swine undergoing thermal ablation, MI swine undergoing no ablation, and healthy swine undergoing similar PFA applications that included linear lesion sets. Tissues were systematically assessed by gross pathology utilizing 2,3,5-triphenyl-2H-tetrazolium chloride staining and histologically with haematoxylin and eosin and trichrome. Pulsed-field ablation in healthy myocardium generated well-demarcated ellipsoid lesions (7.2 ± 2.1 mm depth) with contraction band necrosis and myocytolysis. Pulsed-field ablation in MI demonstrated slightly smaller lesions (depth 5.3 ± 1.9 mm, P = 0.0002), and lesions infiltrated into the irregular scar border, resulting in contraction band necrosis and myocytolysis of surviving myocytes and extending to the epicardial border of the scar. Coagulative necrosis was present in 75% of thermal ablation controls but only in 16% of PFA lesions. Linear PFA resulted in contiguous linear lesions with no gaps in gross pathology. Neither CF nor local R-wave amplitude reduction correlated with lesion size. CONCLUSION: Pulsed-field ablation of a heterogeneous chronic MI scar effectively ablates surviving myocytes within and beyond the scar, demonstrating promise for the clinical ablation of scar-mediated ventricular arrhythmias.

Meta-analysis of catheter ablation in patients with post-infarct cardiomyopathy undergoing defibrillator implantation.

BACKGROUND: Patients with post-infarct cardiomyopathy and ventricular arrhythmias (VT) necessitating implantable cardioverter defibrillators (ICD) are at risk of recurrent shocks with increased morbidity. METHODS: A comprehensive search of electronic databases for all randomized clinical trials that evaluated the role of catheter ablation as a preventive strategy at the time of secondary prevention ICD implantation was performed. We calculated hazard ratios (HR) and 95% confidence intervals (CI) using random-effects model. RESULTS: Four trials were identified with a total of 505 patients (average age 66.4 ± 9.0 years; 87.7% were male). Preventive ablation was associated with a significant reduction in appropriate device therapies (shocks and/or anti-tachycardia therapy) (HR = 0.62; 95% CI = 0.46-0.82; P < .01), sustained VT (HR = 0.74; 95% CI = 0.55-0.99; P = .04) compared to control. There were no differences in inappropriate device shocks (HR = 0.80; 95% CI = 0.38-1.71), all-cause death (HR = 0.93; 95% CI = 0.53-1.64), cardiac death (HR = 0.63; 95% CI = 0.29-1.36), arrhythmic death (HR = 0.26; 95% CI = 0.05-1.31), or cardiac hospitalization (HR = 0.79; 95% CI = 0.57-1.11) between strategies. Preventive ablation was associated with improved SF-36 physical component (mean difference = 2.81; 95% CI-0.53-5.10; P = .02), but not the mental component (mean difference = 1.30; 95% CI = -2.06-4.66). CONCLUSION: Among patients with post-infarct cardiomyopathy and VT, preventive catheter ablation at the time of ICD implantation is associated with a significant reduction of appropriate ICD therapy and sustained VT, and improvement in the physical component of quality-of-life, but no reduction in mortality.

Adverse device-device interaction between pacemaker and subcutaneous implantable cardiac defibrillator.

A 26-year-old patient with prior surgery for Ebstein's anomaly and a pacemaker (placed for post-surgical heart block and poor underlying rhythm) underwent SICD was placement. During defibrillation testing, device-device interaction led to undersensing of ventricular fibrillation with failure to shock. Increasing the pacemaker sensitivity resolved the problem but post shock pacing was unable to capture the heart after both shocks. The patient underwent removal of both the pacemaker and the SICD and placement of a transvenous ICD. Complex device-device interactions can occur in patients who are pacemaker dependent and undergo placement of a SICD.

Imaging-guided cardiac resynchronization therapy: A meta-analysis of randomized controlled trials.

BACKGROUND: Among patients with heart failure and left ventricular (LV) dysfunction despite guideline directed medical therapy, cardiac resynchronization (CRT) is an effective technology to reverse LV remodeling. Given that a large portion of patients are non-responders, alternatives to traditional LV-lead placement have been explored. A promising alternative is image targeted placement of an LV-lead to latest mechanically activated segment without scar. METHODS: Electronic database search for randomized controlled trials (RCTs) that evaluated the imaging-guided LV-lead placement on clinical, echocardiographic, and functional outcomes. The primary outcome was a composite of mortality and heart failure hospitalization. The secondary outcomes included CRT responders, New York Heart Association (NYHA), 6-minute walk test, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and ejection fraction (EF) changes. RESULTS: Analysis included 4 RCTs of 691 patients with an average follow-up of 2 years (age 69.5 ± 10.3 years, 76% males, 54% ischemic cardiomyopathy, 81% with NYHA classes III/IV, and EF of 24.4% ± 8). The most common site for LV-lead paced segment was the anterolateral segment (45%) and at mid-LV (49%). Compared with the control, imaging-guided LV-lead placement was associated with a significant reduction of the primary outcome (hazard ratio [HR] = 0.60; 95% CI = 0.40-0.88; p = .01), higher CRT responders (odd ratio [OR] = 2.10; p < .01), more NYHA improvements by ≥1 (OR = 1.89; p = .01), increased 6MWT (mean difference [MD] = 25.78 feet; p < .01), and lower MLHFQ (MD = -4.04; p = .04), without significant differences in the LVEF (p = .08). CONCLUSIONS: In patients undergoing CRT, imaging-guided LV-lead placement was associated with improved clinical, echocardiographic, and functional status.

Transvenous management of cardiac implantable electronic device late lead perforation.

INTRODUCTION: Late lead perforation (LLP), defined as perforation ≥30 days from cardiac implantable electronic device implant, is a rare diagnosis and little data exist regarding management practices and outcomes. The purpose of this study was to evaluate the occurrence, safety, and efficacy of transvenous management of clinically significant LLP. METHODS: The electronic medical records of a single-center tertiary hospital were reviewed for all patients who were referred for LLP or its sequelae. RESULTS: Eleven consecutive patients were identified from October 2011 to December 2018 with clinically significant LLP. Patients most often presented with pericardial symptoms with the exception of one asymptomatic patient. The median time from lead implant to intervention for LLP was 246 days. Nine patients were managed with an initial transvenous approach, with one requiring sternotomy (lead 6.3 years old). Two patients had a surgical approach, one performed at an outside hospital with subsequent death and another had a mini-thoracotomy, but the lead was removed percutaneously with no surgical repair. In this small cohort, there was no association between the lead extending beyond the parietal pericardium and surgical repair (P = .99). CONCLUSION: Our single-center experience suggests that LLP can be initially managed with a cautious transvenous approach in most patients, but intraprocedural ultrasound for pericardial monitoring and a rescue plan with immediate surgical back up is mandatory.

Atrial arrhythmias in heart failure with a reduced ejection fraction.

PURPOSE OF REVIEW: Atrial arrhythmias are common among individuals with heart failure with a reduced ejection fraction (HFrEF). This review describes management options for these arrhythmias and discusses emerging clinical data supporting catheter ablation. RECENT FINDINGS: Several recent clinical trials indicate that catheter ablation is superior to pharmacologic therapy for management of symptomatic atrial fibrillation in the setting of HFrEF. Restoration and maintenance of sinus rhythm appears to have the greatest benefit with regard to ejection fraction improvement among individuals with a nonischemic heart failure etiology and minimal left ventricular fibrosis. SUMMARY: A rhythm control strategy should be strongly considered in patients with HFrEF, especially when the atrial arrhythmia is symptomatic or is present at the time of a heart failure diagnosis. Catheter ablation may be the preferred strategy for maintenance of sinus rhythm in this patient population.

An automated fractionation mapping algorithm for mapping of scar-based ventricular tachycardia.

BACKGROUND: Mapping and ablation of fractionated electrograms is a common treatment for scar-based ventricular tachycardia (VT). An automated algorithm has been developed for rapid "fractionation mapping." METHODS: Electroanatomic maps from 21 ablation procedures (14 scar-based VT and seven control idiopathic VT/premature ventricular contractions with normal voltage) were retrospectively analyzed using the Ensite Precision fractionation map (fMap; Abbott Laboratories; Abbott Park, IL, USA) algorithm. For each study, voltage maps and 30 fMaps were generated using combinations of parameters: width (5, 10, 20 ms), refractory time (15, 30 ms), sensitivity (0.1, 0.2 mV), and fractionation threshold (2, 3, 5). Parameter sensitivity was assessed by overlap of fractionated areas (fArea) with successful VT ablation sites (defined by entrainment and/or pace mapping). Specificity was assessed by presence of fractionated areas in control patients. RESULTS: Of the 30 fMap parameter sets tested, seven identified >50% of scar-based VT ablation sites, and 26 contained <5 cm2 fractionation on control fMaps. Three combinations of fMap width/refractory/sensitivity/threshold parameters met both of the above criteria, and 20/30/0.1/2 identified the most VT ablation sites (79%) and generated 42.3 ± 28.2 cm2 of fArea on scar-based VT maps compared with 4.9 ± 3.2 cm2 on control maps (P = .001). None of the control patients and 23% of the scar-based VT patients had VT recurrence at mean 15 month follow-up. CONCLUSION: Careful selection of signal processing parameters optimizes sensitivity and specificity of automated fractionation mapping for scar-based VT. Real-time use of fMap algorithms may reduce VT ablation procedure time and improve substrate modification, which may improve outcomes.

The QT Interval as a Noninvasive Marker of Atrial Refractoriness.

BACKGROUND: Atrial refractoriness may be an important determinant of atrial fibrillation (AF) risk, but its measurement is not clinically accessible. Because the QT interval predicts incident AF and the atrium and ventricle share repolarizing ion currents, we investigated the association between an individual's QT interval and atrial effective refractory period (AERP). METHODS: In paroxysmal AF patients presenting for catheter ablation, the QT interval was measured from the surface 12-lead electrocardiogram. The AERP was defined as the longest S1-S2 coupling interval without atrial capture using a 600-ms drive cycle length. RESULTS: In 28 patients, there was a positive correlation between QTc and mean AERP. After multivariate adjustment, a 1-ms increase in QTc predicted a 0.70-ms increase in AERP. CONCLUSIONS: The QTc interval reflects the AERP, suggesting that the QTc interval may be used as a marker of atrial refractoriness relevant to assessing AF risk and mechanism-specific therapeutic strategies.

Therapeutic Ultrasound Promotes Reperfusion and Angiogenesis in a Rat Model of Peripheral Arterial Disease.

BACKGROUND: Shock wave therapy (SWT) is an acoustic technology clinically used for the non-invasive treatment of ischemic heart disease (IHD). Therapeutic ultrasound (TUS) has more recently been developed for the same indication, although its effects on reperfusion and angiogenesis have yet to be directly compared to those of SWT. METHODS AND RESULTS: TUS and SWT acoustic parameters were matched, and their ability to promote angiogenesis and reperfusion in a rat hindlimb ischemia model was compared. After left femoral artery excision, 3-weekly TUS, SWT or sham treatments (n=10 rats each) of the left hindlimb were performed for 2 weeks. Laser Doppler perfusion imaging demonstrated improved perfusion with TUS (66±4% L:R hindlimb perfusion, mean±SEM, P=0.02), but not with SWT (59±4%, P=0.13) compared with sham (50±4%). Immunohistochemistry of CD31 demonstrated increased microvascular density with TUS (222.6 vessels/high-power field, P=0.001) and SWT (216.9, P=0.01) compared to sham-treated rats (196.0). Tissue vascular endothelial growth factor mRNA levels were elevated in the left hindlimb of TUS-, but not SWT- or sham-treated rats. CONCLUSIONS: Direct comparison demonstrates that TUS is more effective than SWT at promoting reperfusion, whereas both therapies promote angiogenesis in ischemic gastrocnemius muscle. These results suggest that TUS may be more effective than SWT for the treatment of IHD and peripheral arterial disease.

Importance of Ventricular Tachycardia Induction and Mapping for Patients Referred for Epicardial Ablation.

BACKGROUND: Many nonischemic cardiomyopathy (NICMP) patients referred for catheter ablation of ventricular tachycardia (VT) undergo an initial epicardial approach under general anesthesia (GA). However, GA may suppress inducibility and decrease tolerance of induced VT, leaving substrate modification as the sole ablation method. OBJECTIVES: Determine the utility of a strategy of initial programmed electrical stimulation (PES) under light sedation in patients referred for epicardial ablation of VT. METHODS: Of 68 NICMP patients referred for VT ablation, 25 were referred specifically for epicardial ablation. All patients underwent PES under conscious sedation, with conversion to GA and epicardial access only if VT morphology and/or endocardial mapping suggested an epicardial substrate. RESULTS: VT was induced with PES in 24 of 25 patients (mean age 52 years; 76% male; ejection fraction 38 ± 18%). VT was hemodynamically tolerated in 63% and unstable in 38% of patients. The noninducible/unstable VT patients underwent substrate modification based on voltage and pace mapping. Of the patients with stable VT, 73% were mapped and ablated endocardially (six right ventricle, three left ventricle, one left coronary cusp, one middle cardiac vein), and 33% were successfully ablated in areas of normal endocardial voltage. After ablation, the clinical VT was noninducible in all patients. After mean follow-up of 10 months, 80% were free of implantable cardioverter defibrillator shocks or sustained VT. CONCLUSIONS: An initial approach of PES and entrainment mapping under conscious sedation is critically important for patients with NICMP referred for epicardial ablation. Empiric ablation of endocardial/epicardial scar would have missed the clinical VT in 20% of patients.

Impact of COVID-19 pandemic on the volume, cost, and outcomes of cardiac electrophysiology procedures in the United States.

BACKGROUND: During the COVID-19 pandemic, professional societies recommended deferral of elective procedures for optimal resource utilization. OBJECTIVE: We sought to assess changes in procedural trends and outcomes of electrophysiology (EP) procedures during the pandemic. METHODS: National Inpatient Sample databases were used to identify all EP procedures performed in the United States (2016-2020) by International Classification of Diseases, Tenth Revision codes. We evaluated trends in utilization, cost/revenue, and outcomes from EP procedures performed. RESULTS: An estimated 1.35 million EP procedures (82% devices and 18% catheter ablations) were performed (2016-2020) with significant yearly uptrend. During the pandemic, there was a substantial decline in EP procedure utilization from a 5-year peak of 298 cases/million population in the second quarter of 2019 to a nadir of 220 cases in the second quarter of 2020. In 2020, the pandemic was associated with the loss of 50,233 projected EP procedures (39,337 devices and 10,896 ablations) with subsequent revenue loss of $7.06 billion. This deficit was driven by revenue deficit from dual-chamber permanent pacemaker (PPM) utilization ($2.88 billion, 49.3% of lost cases), ablation procedures ($1.84 billion, 21.7% of lost cases), and implantable cardioverter-defibrillator implantation ($1.36 billion, 12.0% of lost cases). To the contrary, there was a 9.4% increase in the utilization of leadless PPM. EP device implantation during the pandemic was associated with higher adverse in-hospital events (9.4% vs 8.0%; P < .001). CONCLUSION: In the United States, the significant decline in EP procedures during the pandemic was primarily driven by the reduction in dual-chamber PPM utilization, followed by arrhythmia ablation and implantable cardioverter-defibrillator implantation. There was a substantial increase in leadless PPM utilization during the pandemic.

Impact of concomitant surgical interventions on outcomes of septal myectomy in obstructive hypertrophic cardiomyopathy.

BACKGROUND: Septal myectomy (SM) is offered to symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM) despite medical therapy. Frequently, patients undergo concomitant planned or ad-hoc mitral valve replacement (MVR), aortic valve replacement (SAVR), or coronary artery bypass grafting (CABG). OBJECTIVES: We sought to assess characteristics and outcomes of patients with oHCM undergoing concomitant surgical interventions at the time of SM. METHODS: The National Readmission Databases were used to identify all SM admissions in the United States (2010-2019). Patients undergoing SM were stratified into: isolated SM (±MV repair), SM + CABG only, SM + MVR, SM + SAVR, and SM + MVR + SAVR. Primary outcomes were in-hospital mortality, in-hospital adverse events, and 30-day readmission. RESULTS: 12,063 encounters of patients who underwent SM were included (56.1% isolated SM, 9.0% SM + CABG only, 17.5% SM + MVR, 13.1% SM + SAVR, and 4.3% SM + MVR + SAVR). Patients who underwent isolated SM were younger (54.3 vs. 67.1 years-old, p < 0.01) and had lower overall comorbidity burden. In-hospital mortality was lowest in isolated SM, followed by CABG only, SM + SAVR, SM + MVR, and SM + SAVR+MVR groups (2.3% vs. 3.7% vs. 5.3% vs. 6.7% vs. 13.7%, p < 0.01), respectively. SM with combined surgical interventions was associated with higher adverse in-hospital events (24.3% vs. 11.1%, p < 0.01) and 30-day readmissions (16.9% vs. 10.4%, p < 0.01). MV repair performed concomitantly with SM was not associated with increased in-hospital mortality (3.9% vs. 3.4%, p = 0.72; aOR 0.99; 95% CI: 0.54-1.80, p = 0.97]) or adverse clinical events. CONCLUSIONS: In SM for oHCM, patients undergoing concomitant surgical interventions were characteristically distinct. Aside from MV repair, concomitant interventions were associated with worse in-hospital death, adverse in-hospital events, and 30-day readmission.

Bipolar ablation involving coronary venous system for refractory left ventricular summit arrhythmias.

Background: Catheter ablation of premature ventricular complexes (PVCs) and ventricular tachycardia (VT) from the left ventricular summit (LVS) may require advanced ablation techniques. Bipolar ablation from the coronary veins and adjacent endocardial structures can be effective for refractory LVS arrhythmias. Objective: The aim of this study was to investigate the outcomes of bipolar ablation performed between the coronary venous system and adjacent endocardial left ventricular outflow tract (LVOT) or right ventricular outflow tract (RVOT). Methods: This multicenter study included consecutive patients with LVS PVC/VT who underwent bipolar ablation between the anterior interventricular vein (AIV) or great cardiac vein (GCV) and the endocardial LVOT/RVOT after failed unipolar ablation. Ablation was started with powers of 10-20 W and uptitrated to achieve an impedance drop of at least 10%. Angiography was performed in all cases to confirm a safe distance (>5 mm) of the catheter from the major coronary arteries. Results: Between 2013 and 2023, bipolar radiofrequency ablation between the AIV/GCV and the adjacent LVOT/RVOT was attempted in 20 patients (4 female; age 57 ± 16 years). Unipolar ablation from sites of early activation (AIV/GCV, LVOT, aortic cusps, RVOT) failed to effectively suppress the PVC/VT in all subjects. Bipolar ablation was delivered with a maximum power of 30 ± 8 W and total duration of 238 ± 217 s and led to acute PVC/VT elimination in all patients. No procedural-related complications occurred. Over a follow-up period of 30 ± 24 months, the freedom from arrhythmia recurrence was 85% (1 recurrence in the VT group and 2 in the PVC group). PVC burden was reduced from 22% ± 10% to 4% ± 8% (P <.001). Conclusion: In cases of LVS PVC/VT refractory to unipolar ablation, bipolar ablation between the coronary venous system and adjacent endocardial LVOT/RVOT is safe and effective if careful titration of power and intraprocedural angiography are performed to ensure a safe distance from the coronary arteries.

Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

AIMS: Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. METHODS AND RESULTS: Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. CONCLUSIONS: In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

Mode and Characteristics of Arrhythmia Initiation in Idiopathic Ventricular Fibrillation: A THESIS Substudy.

BACKGROUND: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule. OBJECTIVES: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation. METHODS: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed. RESULTS: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively. CONCLUSIONS: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes.

Urinary albumin concentration and long-term cardiovascular risk in acute coronary syndrome patients: a PROVE IT-TIMI 22 substudy.

Albuminuria has been shown to be associated with mortality and cardiovascular events, independent of traditional cardiovascular risk factors. This suggests that albuminuria may not just represent glomerular damage, but may be a marker of more diffuse endothelial dysfunction. We investigated the relationship between urinary albumin levels after an acute coronary syndrome and cardiovascular outcomes in statin treated subjects after acute coronary syndromes (ACS). Furthermore we assessed the effect of intensive statin treatment on albuminuria among patients in the PROVE IT-TIMI 22 trial, in which patients who had been hospitalized with ACS were randomized to pravastatin 40 mg (standard therapy) or atorvastatin 80 mg daily (intensive therapy). In univariate analyses, increasing urine albumin concentration was associated with increased risk of myocardial infarction, stroke, heart failure, and composite of death, myocardial infarction and stroke at 2 years. However, in a multivariable model containing traditional cardiovascular risk factors, albuminuria was not an independent predictor of the primary PROVE IT endpoint of death, myocardial infarction, unstable angina, revascularization and stroke, and was only an independent predictor of all-cause mortality at urinary albumin concentration >300 mcg/ml. There was no significant change in urinary albumin concentration from enrolment to end of study in either the standard or intensive statin therapy groups, and no significant difference between treatment groups. Our results suggest that after an acute coronary syndrome in statin treated patients, microalbuminuria may reflect traditional cardiovascular risk factor burden and offer little prognostic information independent of those factors.

Efficacy and safety of dofetilide and sotalol in patients with hypertrophic cardiomyopathy.

BACKGROUND: Professional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic cardiomyopathy (HCM), and supporting data is sparse. We aim to assess safety and efficacy of DOF and STL on arrhythmias in HCM. METHODS: This was an observational study of HCM patients treated with DOF or STL for atrial fibrillation (AF) and ventricular arrhythmias (VA). Outcomes of drug discontinuation and arrhythmia recurrence were compared at 1 year and latest follow-up by Kaplan-Meier analysis. Predictors of drug failure were studied using uni- and multi-variable analyses. Drug-related adverse events were quantitated. RESULTS: Here we show that of our cohort of 72 patients (54 ± 14 years old, 75% male), 21 were prescribed DOF for AF, 52 STL for AF, and 18 STL for VA. At 1 year, discontinuation and recurrence rates were similar for DOF-AF (38% and 43%) and STL-AF (29% and 44%) groups. Efficacy data was similar at long-term follow-up of 1603 (IQR 994-4131) days, and for STL-VA. Drug inefficacy was the most common reason for discontinuation (28%) followed by side-effects (13%). Incidences of heart failure hospitalization (5%) and mortality (3%) were low. One STL-AF patient developed non-sustained torsades de pointes in the setting of severe pneumonia and acute kidney injury, but there were no other drug-related serious adverse events. CONCLUSIONS: DOF and STL demonstrate modest efficacy and satisfactory safety when used for AF and VA in HCM patients.

Hypertrophic cardiomyopathy (HCM) is a genetic condition that affects the heart muscle by making it abnormally thick. It often also causes abnormalities in the heartbeat, known as arrhythmias, which can cause symptoms such as dizziness and shortness of breath, or death. Historically it has been advised that some drugs that can affect the heartbeat should not be used in those with HCM, leaving people with HCM to be treated with other drugs that have undesirable side effects. We studied HCM patients who had been prescribed two of the drugs that were advised not to be used, called dofetilide and sotalol. The drugs were found to have been safe and effective over a 4-year period. These results suggest that clinical guidelines should be updated to support the use of these drugs for the treatment of arrhythmias in patients with HCM.