Arrhythmogenic Effects of Cardiac Memory.

Cardiac memory is the term used to describe an interesting electrocardiographic phenomenon. Whenever a QRS complex is wide and abnormal, such as during ventricular pacing, the T waves will also be abnormal and will point to the opposite direction of the wide QRS. If the QRS then normalizes, such as after cessation of ventricular pacing, the T waves will normalize as well, but at a later stage. The period of cardiac memory is the phase between the sudden normalization of the QRS and the eventual and gradual return of the T waves to their baseline morphology. Cardiac memory is assumed to be an innocent electrocardiographic curiosity. However, during cardiac memory, reduction of repolarizing potassium currents increases left ventricular repolarization gradients. Therefore, when cardiac memory occurs in patients who already have a prolonged QT interval (for whatever reason), it can lead to a frank long QT syndrome with QT-related ventricular arrhythmias (torsades de pointes). These arrhythmogenic effects of cardiac memory are not generally appreciated and are reviewed here for the first time.

Polymorphic Ventricular Tachycardia: Terminology, Mechanism, Diagnosis, and Emergency Therapy.

Polymorphic ventricular tachyarrhythmias are highly lethal arrhythmias. Several types of polymorphic ventricular tachycardia have similar electrocardiographic characteristics but have different modes of therapy. In fact, medications considered the treatment of choice for one form of polymorphic ventricular tachycardia, are contraindicated for the other. Yet confusion about terminology, and thus diagnosis and therapy, continues. We present an in-depth review of the different forms of polymorphic ventricular tachycardia and propose a practical step-by-step approach for distinguishing these malignant arrhythmias.

Polymorphic ventricular tachycardia, ischaemic ventricular fibrillation, and torsade de pointes: importance of the QT and the coupling interval in the differential diagnosis.

AIMS: Distinctive types of polymorphic ventricular tachycardia (VT) respond differently to different forms of therapy. We therefore performed the present study to define the electrocardiographic characteristics of different forms of polymorphic VT. METHODS AND RESULTS: We studied 190 patients for whom the onset of 305 polymorphic VT events was available. The study group included 87 patients with coronary artery disease who had spontaneous polymorphic VT triggered by short-coupled extrasystoles in the absence of myocardial ischaemia. This group included 32 patients who had a long QT interval but nevertheless had their polymorphic VT triggered by ectopic beats with short coupling interval, a subcategory termed 'pseudo-torsade de pointes] (TdP). For comparison, we included 50 patients who had ventricular fibrillation (VF) during acute myocardial infarction ('ischaemic VF' group) and 53 patients with drug-induced TdP ('true TdP' group). The QT of patients with pseudo-TdP was (by definition) longer than that of patients with polymorphic VT and normal QT (QTc 491.4 ± 25.2 ms vs. 447.3 ± 55.6 ms, P < 0.001). However, their QT was significantly shorter than that of patients with true TdP (QTc 564.6 ± 75.6 ms, P < 0.001). Importantly, the coupling interval of the ectopic beat triggering the arrhythmia was just as short during pseudo-TdP as during polymorphic VT with normal QT (359.1 ± 38.1 ms vs. 356.6 ± 39.4 ms, P = 0.467) but was much shorter than during true TdP (581.2 ± 95.3 ms, P < 0.001). CONCLUSIONS: The coupling interval helps discriminate between polymorphic VT that occurs despite a long QT interval (pseudo-TdP) and polymorphic arrhythmias striking because of a long QT (true TdP).

Pulmonary Vein Isolation With Ablation Index via Single Transseptal Crossing: Critical Role of Carina Isolation.

AIM: Reconnection of the pulmonary veins (PVs) is the most common reason for the recurrence of atrial fibrillation (AF). The ablation index is a marker of ablation lesion quality that achieves high percentages of first-pass isolation and improved AF ablation results. Most operators use a double transseptal approach with confirmation of PV isolation with a circular mapping catheter. In the present study we aimed to show that an ablation index-guided procedure using a single transseptal approach and ablation catheter only would achieve adequate PV isolation while demonstrating the critical role of the carina in PV isolation. METHOD: Sixty-six (66) consecutive patients with paroxysmal AF were included. Thirty-four (34) patients underwent wide antral circumferential ablation (WACA-only) and 32 underwent WACA+ (WACA + empiric carina isolation). All procedures were performed via single transseptal approach. Pulmonary vein isolation was confirmed with the use of a circular mapping catheter in both groups. RESULTS: Compared to WACA-only, WACA+ increased the odds of PV isolation from 65% to 94% (p=0.011). In the WACA-only procedure, ablation of the carina was needed to achieve PV isolation. At the 18-month follow-up (interquartile range 15.2-20.8 months), freedom from AF was 84% for the entire cohort. CONCLUSIONS: Our study confirmed the high success rate of PV isolation using the ablation index and showed that this can be achieved via a single transseptal crossing. Our study confirmed the role of the carina in PV isolation.

Continuous heart rhythm monitoring using mobile photoplethysmography in ambulatory patients.

BACKGROUND: Wearable devices using photo-plethysmography (PPG) can accurately detect heart beats and may be useful for heart rate measurement and diagnosis of arrhythmias such as atrial fibrillation (AF). A previous study of a new portable PPG sensor (CardiacSense) showed high accuracy in heart rate measurement and AF detection in resting patients. We report a trial done to test the same device in active ambulatory patients with diverse characteristics. METHODS: A cohort of 24 ambulatory volunteers, underwent simultaneous PPG recording and continuous electrocardiogram (ECG) recording under different environmental conditions and situations. Per study protocol, the subjects were diverse in age, BMI, hair density and skin tone. Four subjects had AF. Heart rate measurement using the PPG device was compared to measurements by ECG. RESULTS: Of 163,527 recorded ECG-detected beats in the trial, 86,929 (53.2%) were also recorded by the PPG device. Most undetected heart beats were due to motion induced noise. Correlation between ECG and PPG was high (R = 0.94, p < 0.0001), yet in subjects with AF correlation was lower (R = 0.80, p < 0.0001). A Bland-Altman analysis showed the mean difference between measurements was -0.7 ms (95% limit of agreement -93.8 to 92.2). A total of 86,217 (99.9%) of all RR measurements were reliably measured (RR difference within 100 ms). Reliability was sustained (>99.8%) in subjects of all groups including subjects with AF. CONCLUSIONS: This study showed that, in the absence of movement-related noise, the CardiacSense PPG device can reliably detect HR in a variety of situations and subjects' characteristics.

Continuous heart rate monitoring for automatic detection of atrial fibrillation with novel bio-sensing technology.

BACKGROUND: Asymptomatic atrial fibrillation [AF] is an important cause of fatal or disabling stroke. A continuous heart-rate monitoring device, comfortable enough to be worn continuously and reliable enough to detect AF, would allow for prompt initiation of anticoagulation therapy to prevent stroke. METHODS: We studied a new custom-made wearable photo-plethysmograph [PPG] wrist-watch sensor, specifically designed for continuous heart rate monitoring and incorporating contact and motion noise-filters. We tested its ability to automatically detect AF in patients undergoing elective cardioversion of AF, using simultaneously recorded electrocardiogram [ECG] as gold standard. RESULTS: A total of 18,608 consecutive R-R-interval measurements were recorded simultaneously with PPG and ECG in 20 patients, including 12,521 [67.3%] R-R-intervals during AF and 6087 [32.7%] R-R intervals during sinus rhythm. Scatter plots and Bland-Altman plots demonstrated that the PPG signals were highly correlated to the simultaneously recorded ECG [R = 0.980, p < 0.001], both during AF and during sinus rhythm. The automatic algorithm distinguished AF from sinus rhythm with a sensitivity of 100% and specificity of 93.1%. CONCLUSIONS: This PPG-based wrist-watch sensor reliably detected AF in non-ambulatory patients.

Long-term clinical and echocardiographic follow-up of the freestyle stentless aortic bioprosthesis: the Tel Aviv Medical Center experience.

BACKGROUND: Stentless aortic bioprostheses were designed to provide improved hemodynamic performance and potentially better survival. OBJECTIVES: To report the outcomes of patients after aortic valve replacement with the Freestyle stentless bioprosthesis at the Tel Aviv Medical Center followed for < or = 15 years. METHODS AND RESULTS: Between 1997 and 2011, 268 patients underwent primary aortic valve replacement with a Freestyle bioprosthesis, 211 (79%) of them in the sub-coronary position. Mean age, Charlson comorbidity index and Euro-score were 71.0 +/- 9.2 years, 4.2 +/- 1.5 and 10.2 +/- 11 respectively, and 156 (58%) were male. Peak and mean trans-aortic gradient decreased significantly (75.0 +/- 29.1 vs. 22.8 +/- 9.6 mmHg, P < 0.0001; and 43.4 +/- 17.2 vs. 12.1 +/- 5.4 mmHg, P < 0.0001 respectively) during 3 months of follow-up. Mean overall follow-up was 4.9 +/- 3.1 years and was complete in all patients. In-hospital mortality was 4.1% (n=11) but differed significantly between the first 100 patients operated before 2006 and the last 168 patients operated after January 2006 (8 vs. 3 patients, 8.0% vs. 1.8%, P = 0.01). Overall, 5 and 10 year survival rates were 85 +/- 2.5% and 57.2 +/- 5.7%, respectively. Five year survival was markedly improved in patients operated after January 2006 compared to those operated in the early years of the experience (92.3 +/- 2.3% vs. 76.0 +/- 4.4%, P = 0.0009). All the 21 octogenarians operated after January 2006 survived surgery, with excellent 5 year survival (85.1 +/- 7.9%). Six patients required reoperation during follow-up: structural valve deterioration in five and endocarditis in one. CONCLUSIONS: Aortic valve replacement with the Freestyle bioprosthesis provides good long-term hemodynamic and clinical outcomes, even in octogenarians. Valve calcification is the major (and rare) mode of valve deterioration leading to reoperation in these patients.

Regional Antibiotic Delivery for Implanted Cardiovascular Electronic Device Infections.

BACKGROUND: Present guidelines endorse complete removal of cardiovascular implantable electronic devices (pacemakers/defibrillators), including extraction of all intracardiac electrodes, not only for systemic infections, but also for localized pocket infections. OBJECTIVES: The authors evaluated the efficacy of delivering continuous, in situ-targeted, ultrahigh concentration of antibiotics (CITA) into the infected subcutaneous device pocket, obviating the need for device/lead extraction. METHODS: The CITA group consisted of 80 patients with pocket infection who were treated with CITA during 2007-2021. Of them, 9 patients declined lead extraction because of prohibitive operative risk, and 6 patients had questionable indications for extraction. The remaining 65 patients with pocket infection, who were eligible for extraction, but opted for CITA treatment, were compared with 81 patients with pocket infection and similar characteristics who underwent device/lead extraction as primary therapy. RESULTS: A total of 80 patients with pocket infection were treated with CITA during 2007-2021. CITA was curative in 85% (n = 68 of 80) of patients, who remained free of infection (median follow-up 3 years [IQR: 1.0-6.8 years]). In the case-control study of CITA vs device/lead extraction, cure rates were higher after device/lead extraction than after CITA (96.2% [n = 78 of 81] vs 84.6% [n = 55 of 65]; P = 0.027). However, rates of serious complications were also higher after extraction (n = 12 [14.8%] vs n = 1 [1.5%]; P = 0.005). All-cause 1-month and 1-year mortality were similar for CITA and device/lead extraction (0.0% vs 3.7%; P = 0.25 and 12.3% vs 13.6%; P = 1.00, respectively). Extraction was avoided in 90.8% (n = 59 of 65) of extraction-eligible patients treated with CITA. CONCLUSIONS: CITA is a safe and effective alternative for patients with pocket infection who are unsuitable or unwilling to undergo extraction. (Salvage of Infected Cardiovascular Implantable Electronic Devices [CIED] by Localized High-Dose Antibiotics; NCT01770067).

Reconstruction of the left atrium for atrial fibrillation ablation using the machine learning CARTO 3 m-FAM software.

PURPOSE: Atrial fibrillation (AF) ablation requires a precise reconstruction of the left atrium (LA) and pulmonary veins (PV). Model-based FAM (m-FAM) is a novel module recently developed for the CARTO system which applies machine learning techniques to LA reconstruction. We aimed to evaluate the feasibility and safety of a m-FAM-guided AF ablation as well as the accuracy of LA reconstruction using the cardiac computed tomography angiography (CTA) of the same patient LA as the gold standard, in 32 patients referred for AF ablation. METHODS: Consecutive patients undergoing AF ablation. The m-FAM reconstruction was performed with the ablation catheter (group 1) or a Pentaray and ablation catheters (group 2). The reconstruction accuracy was confirmed prior to the ablation by verification of pre-specified landmarks of the LA and PVs by an intracardiac echocardiogram (ICE) visualization and fluoroscopy. A cardiac CTA performed before the ablation was used as the gold standard of LA anatomy. For each patient, the m-FAM reconstruction was compared to his/her cardiac CTA. RESULTS: The m-FAM reconstruction was accurate in all patients regardless of the catheter used for mapping. Twelve percent re-acquisition of the LA landmarks was necessary to improve the accuracy. m-FAM time was shorter in group 2 while the M-Fam fluoroscopy time was similar. Pulmonary vein isolation was achieved in 100% of patients without major complications. The m-FAM reconstructions accurately resemble the cardiac CTA of the same patients. CONCLUSIONS: The m-FAM module allows for rapid and precise reconstruction of the LA and PV anatomy, which can be safely used to guide AF ablation.

Implantation of cardiac electronic devices in active COVID-19 patients: Results from an international survey.

BACKGROUND: Cardiac implantable electronic device (CIED) implantation rates as well as the clinical and procedural characteristics and outcomes in patients with known active coronavirus disease 2019 (COVID-19) are unknown. OBJECTIVE: The purpose of this study was to gather information regarding CIED procedures during active COVID-19, performed with personal protective equipment, based on an international survey. METHODS: Fifty-three centers from 13 countries across 4 continents provided information on 166 patients with known active COVID-19 who underwent a CIED procedure. RESULTS: The CIED procedure rate in 133,655 hospitalized COVID-19 patients ranged from 0 to 16.2 per 1000 patients (P <.001). Most devices were implanted due to high-degree/complete atrioventricular block (112 [67.5%]) or sick sinus syndrome (31 [18.7%]). Of the 166 patients in the study survey, the 30-day complication rate was 13.9% and the 180-day mortality rate was 9.6%. One patient had a fatal outcome as a direct result of the procedure. Differences in patient and procedural characteristics and outcomes were found between Europe and North America. An older population (76.6 vs 66 years; P <.001) with a nonsignificant higher complication rate (16.5% vs 7.7%; P = .2) was observed in Europe vs North America, whereas higher rates of critically ill patients (33.3% vs 3.3%; P <.001) and mortality (26.9% vs 5%; P = .002) were observed in North America vs Europe. CONCLUSION: CIED procedure rates during known active COVID-19 disease varied greatly, from 0 to 16.2 per 1000 hospitalized COVID-19 patients worldwide. Patients with active COVID-19 infection who underwent CIED implantation had high complication and mortality rates. Operators should take these risks into consideration before proceeding with CIED implantation in active COVID-19 patients.

Continuous Heart Rate Monitoring for Automatic Detection of Life-Threatening Arrhythmias With Novel Bio-Sensing Technology.

Aims: Assessing the effectiveness of novel bio-sensing technology (CardiacSense), for accuracy and reliability of automatic detection of life-threatening arrhythmias. Methods and Results: This prospective study consisted of Eighteen patients (13 males and 5 females, mean age 59.4 ± 21.3 years) undergoing induction of ventricular tachycardia/fibrillation or provocation of transient ventricular asystole. We tested the detection of provoked ventricular arrhythmias by a wrist-worn watch-like device which uses photoplethysmography (PPG) technology to detect the cardiac rhythm. We used simultaneous electrocardiographic (ECG) recordings as gold standard for arrhythmia definition and confirmation of beat-to-beat detection. A total of 1,527 QRS complexes were recorded simultaneously by ECG and PPG. The overall correlation between the ECG (R-R intervals) and the PPG (G-G intervals) was high, with a correlation coefficient of R = 0.949 (p < 0.001). The device accurately detected all events of mimicked life endangering arrhythmias, including five events of transient (adenosine-induced) ventricular asystole as well as seven episodes of monomorphic ventricular tachycardia and 6 events of ventricular fibrillation. Conclusion: This proof-of-concept study suggests that wearable devices using PPG technology, currently used to detect atrial fibrillation, may also have a role as automatic detectors of life-threatening arrhythmias.

Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome.

BACKGROUND: The list of medications linked to drug-induced long QT syndrome (LQTS) is diverse. It is possible that food products too have QT-prolonging potential. OBJECTIVE: We tested the effects of grapefruit juice on the QT interval with the methodology used by the pharmaceutical industry to test new drugs. METHODS: This was an open-label, randomized, crossover study with blinded outcome evaluation, a thorough QT study of grapefruit juice performed according to the Guidelines for the Clinical Evaluation of QT/QTc for Non-antiarrhythmic Drugs. Thirty healthy volunteers and 10 patients with congenital LQTS were studied. Healthy volunteers drank 2 L of grapefruit juice (in divided doses), or received 400 mg oral moxifloxacin, in a randomized crossover study. Patients with LQTS were tested with only grapefruit. Repeated baseline, off-drug, and on-drug (grapefruit or moxifloxacin) electrocardiograms were scanned and coded. QT measurements were done with electronic calipers. RESULTS: In comparison to off-drug electrocardiograms, grapefruit juice led to significant rate-corrected QT (QTc) prolongation. The absolute net QTc prolongation from grapefruit was 14.0 ms (95% confidence interval 6.2-21.7 ms; P < .001). The QT-prolonging effects of grapefruit in healthy volunteers were comparable with those of moxifloxacin. The QT-prolonging effects of grapefruit juice were greater in female patients and particularly marked in patients with LQTS (net QTc prolongation 21.8 ms; 95% confidence interval 3.4-35.3 ms; P = .034). CONCLUSION: Grapefruit juice, at doses tested, prolongs the QT interval. The effect is significant in healthy volunteers, greater in female patients, and more so in patients with LQTS.

Sustained Elevation of Vascular Endothelial Growth Factor and Angiopoietin-2 Levels After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes the systemic vasculature to increased mechanical forces. Endothelial adaptation to mechanical stimuli is associated with angiogenic activation through various growth factors. We studied the potential angiogenic shift evoked by TAVR. METHODS: From a cohort of 69 consecutive patients undergoing TAVR, we excluded patients with conditions known to affect angiogenic factors, and serum vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 were assessed by ELISA. We assessed in vitro the properties of endothelial cells after exposure to serum collected from patients undergoing TAVR using adhesion, migration, and Matrigel angiogenesis assays. The correlation between changes in angiogenic factors and cardiac functions was evaluated on 30- day echocardiograms. RESULTS: The study population consisted of 46 patients (82 ± 5 years). Two days after TAVR the post/pre TAVR ratio of VEGF, Ang-1, and Ang-2 was 5.38 ± 4 (P < 0.001), 1.05 ± 0.49 (P = 0.27), and 4.65 ± 2.01 (P < 0.001), respectively. The increase in VEGF and Ang-2 showed a significant correlation (r = 0.609; P < 0.001), but no correlation was found with hemolysis or tissue injury markers. Patients with relatively low levels of VEGF or an Ang-2 rise had more severe aortic stenosis and coronary disease at baseline. Exposure of endothelial cells to post-TAVR serum induced adhesion, migration, and tube formation compared with pre-TAVR serum. An increase in VEGF levels correlated with improvement in pulmonary systolic pressure and a right ventricular fractional area change at 30 days, (r = 0.54 and r = 0.48, respectively; P < 0.01). CONCLUSIONS: Sustained elevation of VEGF and Ang-2 levels occur after TAVR, reflecting a systemic angiogenic shift. A rise in VEGF levels is associated with a decrease in pulmonary blood pressure in patients undergoing TAVR.

Hemodynamic performance and outcome of percutaneous versus surgical stentless bioprostheses for aortic stenosis with anticipated patient-prosthesis mismatch.

OBJECTIVES: We aimed to compare the performance and midterm survival of transcutaneous aortic valve replacement (TAVR) and surgically implanted stentless aortic valve replacement (SAVR) for severe aortic stenosis in patients anticipated to have patient-prosthesis mismatch (PPM). METHODS: A retrospective analysis was performed of 86 and 49 consecutive TAVR and SAVR patients with severe aortic stenosis and calculated minimal effective orifice area larger than the best projected effective orifice area. Cox hazard analyses were used to assess the effect of TAVR versus SAVR on outcome. RESULTS: The peak and mean transprosthetic gradient at discharge were lower (P < .001 for both) in the TAVR group. Mild or greater aortic regurgitation was more frequent in the TAVR group (61% vs 7%; P < .0001). At 3 months of follow-up, the mean gradient in the TAVR group was similar to that of the SAVR group but the prevalence of aortic regurgitation was still higher. The unadjusted 3-year survival rate was superior in the SAVR versus TAVR group (91.6% ± 4% vs 67.0% ± 7%; P = .01). Adjustments for both age and comorbidity resulted in loss of the difference in mortality between the 2 groups. CONCLUSIONS: In patients with anticipated PPM, TAVR offers an immediate lower incidence of PPM than SAVR but a greater prevalence of aortic regurgitation. The differences in transaortic gradients became nonsignificant 3 months postoperatively. The question of whether TAVR is a suitable substitute for SAVR in patients with anticipated PPM, in particular, those who are older and sicker, warrants additional investigation.

Forced diuresis with matched hydration in reducing acute kidney injury during transcatheter aortic valve implantation (Reduce-AKI): study protocol for a randomized sham-controlled trial.

BACKGROUND: Acute kidney injury (AKI) is observed in up to 41% of patients undergoing transcatheter aortic valve implantation (TAVI) and is associated with increased risk for mortality. The aim of the present study is to evaluate whether furosemide-induced diuresis with matched isotonic intravenous hydration using the RenalGuard system reduces AKI in patients undergoing TAVI. METHODS/DESIGN: Reduce-AKI is a randomized sham-controlled study designed to examine the effect of an automated matched hydration system in the prevention of AKI in patients undergoing TAVI. Patients will be randomized in a 1:1 fashion to the RenalGuard system (active group) versus non-matched saline infusion (sham-controlled group). Both arms receive standard overnight saline infusion and N-acetyl cysteine before the procedure. DISCUSSION: The Reduce-AKI trial will investigate whether the use of automated forced diuresis with matched saline infusion is an effective therapeutic tool to reduce the occurrence of AKI in patients undergoing TAVI. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01866800, 30 April 30 2013.