His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy vs Biventricular Pacing: HOT-CRT Clinical Trial.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) using His bundle pacing (HBP) or left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy (CRT). OBJECTIVES: The aim of the study was to compare the feasibility and clinical efficacy of HOT-CRT (His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy) with BVP in patients with heart failure, reduced ejection fraction, and indication for CRT. METHODS: This was a prospective, randomized, controlled trial of HOT-CRT and BVP in patients with LVEF <50% and indications for CRT. If HPCSP resulted in incomplete electrical resynchronization, a coronary sinus (CS) lead was added. The primary outcome was the change in left ventricular ejection fraction (LVEF) at 6 months. The primary safety endpoint was freedom from major complications. RESULTS: A total of 100 patients (female 31%, aged 70 ± 12 years, LVEF 31.5% ± 9.0%) were randomized. HOT-CRT was successful in 48 of 50 (96%) and BVP-CRT in 41 of 50 (82%) patients (P = 0.03). QRS duration significantly decreased from 164 ± 26 ms to 137 ± 20 ms with HOT-CRT and 166 ± 28 ms to 141 ± 19 ms with BVP. Fluoroscopy results (18.8 ± 12.4 min vs 23.8 ± 12.4 min, P = 0.05) and procedure duration (119 ± 42 min vs 114 ± 36 min, P = 0.5) were similar. The primary outcome of change in LVEF at 6 months was greater in HOT-CRT than in BVP (12.4% ± 7.3% vs 8.0% ± 10.1%, P = 0.02). The primary safety endpoint was similar (98% vs 94%, P = 0.62). Echocardiographic response of improvement in LVEF >5% occurred in 80% vs 61% (P = 0.06). Complications occurred in 3 (6%) in HOT-CRT vs 10 (20%) in BVP (P = 0.03). CONCLUSIONS: HPCSP-guided CRT resulted in greater change in LVEF compared with BVP. Randomized clinical trials with long-term follow-up are necessary. (His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy [HOT-CRT]; NCT04561778).

Giant Interventricular Septal Hematoma Complicating Left Bundle Branch Pacing: A Cautionary Tale.

An 88-year-old woman underwent atrioventricular node ablation and left bundle branch pacing for atrial fibrillation. She presented to the emergency room several hours after discharge with dyspnea. An echocardiogram revealed a giant interventricular septal hematoma. The patient was successfully treated with conservative medical therapy, with eventual complete resolution of the hematoma. (Level of Difficulty: Intermediate.).

Coronary and Structural Heart Disease Interventions During COVID-19 Pandemic: A Road Map for Clinicians and Health Care Delivery Systems.

BACKGROUND: Because of the COVID-19 pandemic, cath labs have had to modify their workflow for elective and urgent patients. METHODS: We surveyed 16 physicians across 3 hospitals in our healthcare system to address COVID-19 related concerns in the management of interventional and structural heart disease patients, and to formulate system wide criteria for deferring cases till after the pandemic. RESULTS: Our survey yielded common concerns centered on the need to protect patients, cath lab staff and physicians from unnecessary exposure to COVID-19; for COVID-19 testing prior to arrival to the cath lab; for clear communication between the referring physician and the interventionalist; but there was initial uncertainty among physicians regarding the optimal management of ST elevation myocardial infarction (STEMI; percutaneous coronary intervention versus thrombolytics). Patients with stable angina and hemodynamically stable acute coronary syndromes were deemed suitable for initial medical management, except when they had large ischemic burden. Most transcatheter aortic valve implantations (TAVI) were felt appropriate for postponement except in symptomatic patients with aortic valve area <0.5 cm2 or recent hospitalization for heart failure (HF). Most percutaneous mitral valve repair (pMVR) procedures were felt appropriate for postponement except in patients with HF. All left atrial appendage closure (LAAC) and patent foramen ovale (PFO)/atrial septal defect (ASD) closure procedures were felt appropriate for postponement. CONCLUSION: Our survey of an experienced team of clinicians yielded concise guidelines to direct the management of CAD and structural heart disease patients during the initial phases of the COVID-19 pandemic.

Efficiency, Safety, and Quality of Life After Transcatheter Aortic Valve Implantation Performed With Moderate Sedation Versus General Anesthesia.

There is growing interest in "minimalist" transcatheter aortic valve implantation (M-TAVI), performed with conscious sedation instead of general anesthesia (GA-TAVI). We assessed the impact of M-TAVI on procedural efficiency, long-term safety, and quality of life (QoL) in 477 patients with severe aortic stenosis (82 years, women 50%, STS 5.0), who underwent M-TAVI (n = 278) or GA-TAVI (n = 199). M-TAVI patients were less likely to have NYHA Class ≥3, valve-in-valve TAVI, and receive self-expanding valves. M-TAVI was completed without conversion to GA in 269 (97%) patients. M-TAVI was more efficient that GA-TAVI including shorter lengths of stay (2 vs 3 days, p <0.0001), higher likelihood of being discharged home (87% vs 72%, p <0.0001), less use of blood transfusions (10% vs 22%, p = 0.0008), inotropes (13% vs 32%, p <0.0001), contrast volume (50 vs 90 ml, p <0.0001), fluoroscopy time (20 vs 24 minute, p <0.0001), and need for >1 valves (0.4 vs 5.5%, p = 0.0004). At 1-month, death/stroke (M-TAVI vs GA-TAVI 4.0 vs 6.5%) and a "safety composite" end point (death, stroke, transient ischemic attack, myocardial infarction, new dialysis, major vascular complication, major or life-threatening bleeding, and new pacemaker: 17.6% vs 21.1%) were similar (p = NS for both). At a median follow-up of 365 days, survival curves showed similar incidence of death/stroke as well as the safety composite end point between the groups. QoL scores were similar at baseline and 1-month after TAVI. In multivariable analyses, M-TAVI showed significant improvements in all parameters of procedural efficiency. In conclusion, M-TAVI is more efficient than GA-TAVI, with similar safety at 1-month and long-term, and similar QoL scores at 1 month.

Left bundle branch pacing utilizing three dimensional mapping.

INTRODUCTION: Permanent His bundle pacing is feasible and effective in patients with atrioventricular block or left bundle branch block. However, pacing thresholds to capture the distal His bundle is often higher. Recently left bundle branch area pacing (LBBP) has been shown to be feasible by advancing the lead transvenously, deep into the interventricular septum to reach the left ventricular endocardial surface. In this article we describe the utility of three dimensional (3D) mapping to achieve LBBP. METHODS: Ensite Precision (Abbott) mapping system was used to perform LBBP. A decapolar catheter was used to create 3D map of right atrium and right ventricle (RV). Regions of interest (His bundle, potential LBBP sites of interest in RV) were tagged in the 3D map. The LBBP lead was implanted utilizing the 3D map. The lead depth in the septum was assessed in the 3D map. RESULTS: LBBP was performed in three patients: chronic LBBB and intermittent 2:1 atrioventricular block; atrioventricular (AV) node ablation and conduction system pacing; and bifascicular block and intermittent AV block in a patient with severe left ventricular hypertrophy. LBBP was successful in all three patients. The lead depth in the interventricular septum was 12, 11, and 21 mm, respectively as assessed by 3D mapping. CONCLUSIONS: Three-dimensional mapping was helpful in achieving LBBP in patients with LBBB, severe left ventricular hypertrophy or during AV node ablation. 3D mapping also facilitated easy assessment of lead depth during and after lead fixation. 3D mapping techniques may be a valuable tool to reduce the learning curve of implanters with minimal experience in LBBP.

Prospective evaluation of feasibility and electrophysiologic and echocardiographic characteristics of left bundle branch area pacing.

BACKGROUND: His bundle pacing (HBP) is the most physiologic form of pacing but associated with higher thresholds and lower success in patients with His-Purkinje conduction disease. Recent reports have described transvenous left bundle branch area pacing (LBBAP). OBJECTIVE: We aimed to prospectively evaluate the feasibility and the electrophysiologic and echocardiographic characteristics of LBBAP. METHODS: Patients requiring pacing for bradycardia or heart failure indications (failed left ventricular [LV] lead) were prospectively enrolled. LBBAP was performed with a Medtronic 3830 lead. Presence of left bundle branch (LBB) potential, paced QRS morphology/duration, and peak LV activation time (pLVAT) were recorded at implant. Pacing threshold and sensing was assessed at implant and follow-up. Echocardiography was performed to assess the approximate lead location and impact on tricuspid valve function. RESULTS: LBBAP was successful in 93 of 100 (93%) patients. Mean age was 75 ± 13 years; men 69%, left bundle branch block 24%, right bundle branch block 25%, intraventricular conduction defect 8%. Indications for pacing were atrioventricular (AV) block 54%, sinus node dysfunction 23%, AV node ablation 7%, cardiac resynchronization therapy 11%, HBP lead failure 7%. Baseline QRS duration was 133 ± 35 ms. Paced QRS duration was 136 ± 17 ms. LBB potentials were observed in 63 patients with left bundle branch - ventricle (LBB-V) interval of 27 ± 6 ms. pLVAT was 75 ± 16 ms. Pacing threshold at implant was 0.6 ± 0.4 V @ 0.5 ms and R waves were 10 ± 6 mV and remained stable at median follow-up of 3 months. The lead depth in the septum was approximately 1.4 ± 0.23 cm. CONCLUSIONS: LBBAP was feasible in a high percentage of patients with low thresholds during acute follow-up. HBP and LBBAP may significantly increase the overall success of physiologic pacing.

Left atrial appendage occlusion: 2016 in review.

A significant body of data has emerged in the area of Percutaneous Left Atrial Appendage Occlusion (LAAO). In this article, we present an overview of the most notable publications along with a review of the most important publications on LAAO in 2016. We also present important historical data such as landmark clinical studies, review of most utilized occlusion devices, and important clinical studies that are underway.

Effects of the surface physico-chemical properties and the surface textures on the initial colonization and the attached growth in algal biofilm.

BACKGROUND: Algal biofilm reactors represent a promising cultivation system that can economically produce biomass without the need for expensive harvesting operations. A critical component of algal biofilm systems is the material used for attachment. This research reports a comprehensive study of the effects of material surface physico-chemical properties, the surface texture, and their interactions on the initial colonization and the long-term attached growth in algal biofilm systems. A total of 28 materials with a smooth surface were tested for initial cell colonization and it was found that the tetradecane contact angle of the materials had a good correlation with cell attachment. The effects of surface texture were evaluated using mesh materials (nylon, polypropylene, high-density polyethylene, polyester, aluminum, and stainless steel) with openings ranging from 0.05 to 6.40 mm. RESULTS: The mesh materials with an opening of 0.5 mm resulted in the highest attachment. The interaction of surface physico-chemical properties and surface texture, and their co-effects on the cell attachment, was quantitatively described using a second-order polynomial regression. The long-term algal attached growth for the different materials showed a trend similar to that found in initial colonization. CONCLUSIONS: Collectively, nylon and polypropylene mesh with 0.50-1.25 mm openings resulted in the best initial colonization and long-term attached growth, with a 28-30 g m(-2) biomass yield and 4.0-4.3 g m(-2) day biomass productivity being achieved on a pilot-scale revolving algal biofilm system.

Evaluating algal growth performance and water use efficiency of pilot-scale revolving algal biofilm (RAB) culture systems.

A Revolving Algal Biofilm (RAB) growth system in which algal cells are attached to a flexible material rotating between liquid and gas phases has been developed. In this work, different configurations of RAB systems were developed at pilot-scale by retrofitting the attachment materials to a raceway pond (2000-L with 8.5 m(2) footprint area) and a trough reservoir (150 L with 3.5 m(2) footprint area). The algal growth performance and chemical composition, as well as the water evaporative loss and specific water consumption were evaluated over a period of nine months in a greenhouse environment near Boone, Iowa USA. Additionally a raceway pond was run in parallel, which served as a control. On average the raceway-based RAB and the trough-based RAB outperformed the control pond by 309% and 697%, respectively. A maximum productivity of 46.8 g m(-2) day(-1) was achieved on the trough-based RAB system. The evaporative water loss of the RAB system was modeled based on an energy balance analysis and was experimentally validated. While the RAB system, particularly the trough-based RAB, had higher water evaporative loss, the specific water consumption per unit of biomass produced was only 26% (raceway-based RAB) and 7% (trough-based RAB) of that of the control pond. Collectively, this research shows that the RAB system is an efficient algal culture system and has great potential to commercially produce microalgae with high productivity and efficient water use.

Frequency of coronary angiography and revascularization among men and women with myocardial infarction and their relationship to mortality at one year: an analysis of the Geisinger myocardial infarction cohort.

OBJECTIVES: To determine sex bias in the selection of strategies to evaluate patients with acute myocardial infarction (AMI), and determine if the choice of strategy influences survival. BACKGROUND: Controversy exists regarding the role of female sex in the use of invasive evaluation for AMI and its possible effect on adverse outcomes. METHODS: Electronic health record data from the Geisinger Acute Myocardial Infarction Cohort (GAMIC) was analyzed which included 1,968 men and 1,047 women admitted to the Geisinger Medical Center between January 2001 and December 2006 with acute myocardial infarction (AMI).Multivariate logistic regression analyses were used to determine independent correlates of an invasive evaluation. Multivariate logistic regression modeling stratified on sex was used to determine when invasive evaluation was done and whether there was a correlation with mortality. RESULTS: In unadjusted analyses, male sex was a significant predictor for the use of invasive evaluation (odds ratio = 1.71, 95% CI = [1.46, 2.00]). Adjusted for baseline differences (like age, renal function, co-morbid conditions) multivariate analyses found no significant relationship between male sex and invasive evaluation (OR = 1.02, 95% CI = [0.82, 1.23]). Females in the STEMI group were found to be less revascularized. No difference was observed in the one-year mortality between women and men regardless of invasive evaluation or revascularization. CONCLUSIONS: Sex was not independently associated with the occurrence of an invasive evaluation of a MI. Females in the STEMI group were less revascularized. There was no strong gender effect on survival irrespective of the performance on an invasive evaluation or revascularization.

Transthoracic Doppler echocardiography to noninvasively assess coronary vasoconstrictor and dilator responses in humans.

Human studies of coronary circulation are limited because of methodological issues. Recently, a noninvasive transthoracic duplex ultrasound (TTD) technique has emerged as an important tool to measure coronary blood flow velocity (CBV) in conscious humans. We employed two protocols to determine whether noninvasive "native" coronary artery velocity responses to constrictor or dilator stimuli assessed by TTD provide reliable data. In the first protocol, coronary vascular resistance (CVR = diastolic blood pressure/CBV) responses to static handgrip were examined in the left internal mammary artery (LIMA) and native left anterior descending artery (LAD) into which the graft was inserted (patient age 63 +/- 3 years). Our prior report documented increased CVR in the LIMA graft during static handgrip (Momen et al., J Appl Physiol 102: 735-739, 2007). We hypothesized that the magnitude of increases in CVR during handgrip would be similar in the LIMA graft and LAD in the same individual. Percent increases in CVR were similar in the LIMA and distal native LAD (27 +/- 4% vs. 28 +/- 6%). In the second protocol, we studied six patients (age 61 +/- 3 years) who underwent cardiac catheterization of the LAD. We compared coronary vasodilator responses to intravenous adenosine infusion (0.14 mg.kg(-1).min(-1)) obtained by intracoronary Doppler guidewire technique and TTD on separate studies. The relative increases in CBV with adenosine obtained by intracoronary Doppler guidewire and TTD were similar (62 +/- 10% vs. 65 +/- 12%). Noninvasive TTD provides reliable human coronary circulatory constrictor and dilator data.

Coronary blood flow responses to physiological stress in humans.

Animal reports suggest that reflex activation of cardiac sympathetic nerves can evoke coronary vasoconstriction. Conversely, physiological stress may induce coronary vasodilation to meet an increased metabolic demand. Whether the sympathetic nervous system can modulate coronary vasomotor tone in response to stress in humans is unclear. Coronary blood velocity (CBV), an index of coronary blood flow, can be measured in humans by noninvasive duplex ultrasound. We studied 11 healthy volunteers and measured beat-by-beat changes in CBV, blood pressure, and heart rate during 1) static handgrip for 20 s at 10% and 70% of maximal voluntary contraction; 2) lower body negative pressure at -10 and -30 mmHg for 3 min each; 3) cold pressor test for 90 s; and 4) hypoxia (10% O(2)), hyperoxia (100% O(2)), and hypercapnia (5% CO(2)) for 5 min each. At the higher level of handgrip, mean blood pressure increased (P < 0.001), whereas CBV did not change [P = not significant (NS)]. In addition, during lower body negative pressure, CBV decreased (P < 0.02; and P < 0.01, for -10 and -30 mmHg, respectively), whereas blood pressure did not change (P = NS). The dissociation between the responses of CBV and blood pressure to handgrip and lower body negative pressure is consistent with coronary vasoconstriction. During hypoxia, CBV increased (P < 0.02) and decreased during hyperoxia (P < 0.01), although blood pressure did not change (P = NS), suggesting coronary vasodilation during hypoxia and vasoconstriction during hyperoxia. In contrast, concordant increases in CBV and blood pressure were noted during the cold pressor test, and hypercapnia had no effects on either parameter. Thus the physiological stress known to be associated with sympathetic activation can produce coronary vasoconstriction in humans. Contrasting responses were noted during systemic hypoxia and hyperoxia where mechanisms independent of autonomic influences appear to dominate the vascular end-organ effects.

Cyclooxygenase inhibition attenuates sympathetic responses to muscle stretch in humans.

Passive muscle stretch performed during a period of post-exercise muscle ischemia (PEMI) increases muscle sympathetic nerve activity (MSNA), and this suggests that the muscle metabolites may sensitize mechanoreceptors in healthy humans. However, the responsible substance(s) has not been studied thoroughly in humans. Human and animal studies suggest that cyclooxygenase products sensitize muscle mechanoreceptors. Thus we hypothesized that local cyclooxygenase inhibition in exercising muscles could attenuate MSNA responses to passive muscle stretch during PEMI. Blood pressure (Finapres), heart rate, and MSNA (microneurography) responses to passive muscle stretch were assessed in 13 young healthy subjects during PEMI before and after cyclooxygenase inhibition, which was accomplished by a local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased prostaglandin synthesis to approximately 34% of the baseline. Before ketorolac Bier block, passive muscle stretch evoked significant increases in MSNA (P < 0.005) and mean arterial blood pressure (P < 0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P = 0.11) or mean arterial blood pressure (P = 0.83). Saline Bier block had no effect on the MSNA or blood pressure response to ischemic stretch. These observations indicate that cyclooxygenase inhibition attenuates MSNA responses seen during PEMI and suggest that cyclooxygenase products sensitize the muscle mechanoreceptors.

Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans.

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG, and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of postexercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e., wrist dorsiflexion) was performed. The static stretch protocol was also performed during 1) a freely perfused condition, 2) ischemia alone, and 3) PEMI after nonfatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 +/- 74 to 673 +/- 90 U/min, P < 0.01) and mean blood pressure (102 +/- 2 to 106 +/- 2 mmHg, P < 0.001). Static stretch performed under the other three conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased above a certain threshold.

The role of the cyclooxygenase products in evoking sympathetic activation in exercise.

Animal studies suggest that prostaglandins in skeletal muscles stimulate afferents and contribute to the exercise pressor reflex. However, human data regarding a role for prostaglandins in this reflex are varied, in part because of systemic effects of pharmacological agents used to block prostaglandin synthesis. We hypothesized that local blockade of prostaglandin synthesis in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing exercise. Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 12 young healthy subjects during static handgrip and postexercise muscle ischemia (PEMI) before and after local infusion of 6 mg of ketorolac tromethamine in saline via Bier block (regional intravenous anesthesia). In the second experiment (n = 10), the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased the prostaglandins synthesis to approximately 33% of the baseline. After ketorolac Bier block, the increases in MSNA from the baseline during the fatiguing handgrip was significantly lower than that before the Bier block (before ketorolac: Delta502 +/- 111; post ketorolac: Delta348 +/- 62%, P = 0.016). Moreover, the increase in total MSNA during PEMI after ketorolac was significantly lower than that before the Bier block (P = 0.014). Saline Bier block had no similar effect. The observations indicate that blockade of prostaglandin synthesis attenuates MSNA responses seen during fatiguing handgrip and suggest that prostaglandins contribute to the exercise pressor reflex.