Efficacy of medical and ablation therapy for inappropriate sinus tachycardia: A single-center experience.

BACKGROUND: Effective therapy for inappropriate sinus tachycardia (IST) remains challenging with high rates of treatment failure and symptom recurrence. It is uncertain how effective pharmacotherapy and procedural therapy are long-term, with poor response to medical therapy in general. METHODS: We retrospectively reviewed all patients with the diagnosis of IST at a tertiary academic medical center from 1998 to 2018. We extracted data related to prescribing patterns and symptom response to medical therapy and sinus node modification (SNM), assessing efficacy and periprocedural complication rates. RESULTS: A total of 305 patients with a formal diagnosis of IST were identified, with 259 (84.9%) receiving at least one prescription medication related to the condition. Beta-blockers were the most commonly used medication (n = 245), with a majority of patients reporting no change or worsening of symptoms, and poor response was seen to other medication classes. Improvement was seen significantly more often with ivabradine than beta blockers, though the sample size was limited (p = .003). Fifty-five patients (18.0% of all IST patients), mean age 32.0 ± 9.1 years, underwent a SNM procedure, with an average of 1.8 ± 0.9 procedures per patient. Acute symptomatic improvement (<6 months) was seen in 58.2% of patients. Long-term complete resolution of symptoms was seen in 5.5% of patients, modest improvement in 29.1%, and no long-term benefit was seen in 65.5% of patients. CONCLUSIONS: Among all medical therapies, there were high rates of treatment failure or symptom worsening in over three-quarters of patients in our study. Ivabradine was most beneficial, though the sample size was small. While most patients receiving SNM ablation for IST perceive an acute symptomatic improvement, almost two-thirds of patients have no long-term improvement, and resolution of symptoms is quite rare. AV node ablation with pacemaker implantation following lack of response to SNM offered increased success, though the sample size was limited.

Sinus rhythm heart rate increase after atrial fibrillation ablation is associated with lower risk of arrhythmia recurrence.

BACKGROUND: Pulmonary vein isolation (PVI) with autonomic modulation may be more successful than PVI alone for atrial fibrillation (AF) ablation and may be signaled by changes in sinus rhythm heart rate (HR) post ablation. We sought to determine if a change in sinus rhythm HR predicted AF recurrence post PVI. METHODS: Patients who underwent AF ablation from 2000 to 2011 were included if sinus rhythm was noted on ECG within 90 days pre and 7 days post ablation. Basic ECG interval and HR changes were analyzed and outcomes determined. RESULTS: A total of 1152 patients were identified (74.3% male, mean age 57 ± 11 years). Mean AF duration was 5.2 ± 5.3 years. Paroxysmal AF was noted in 712 (61.8%) of the patients. Mean EF was 61% ± 6%. Sinus rhythm HR was 61 ± 11 pre-ablation and 76 ± 13 bpm post-ablation (27% ± 24% increase, p < .001). The ability of relative HR change post-ablation to predict AF recurrence was borderline (hazard ratio 0.65 [0.41-1.01], p = .067). With patients separated into quartiles based on the relative HR change, the upper quartile with the largest relative increase in HR had a significantly lower rate of AF recurrence compared to the lowest quartile following multi variable modeling (p = .038). There were significant changes in PR (171 ± 28 to 167 ± 30 ms) and QTc (424 ± 25 to 434 ± 29 ms) intervals (both p < .001) but these were not predictive of outcome. CONCLUSION: Relative changes in HR post AF ablation correlates with AF recurrence. Further prospective studies are needed to confirm this relationship.

Natural history and clinical outcomes of inappropriate sinus tachycardia.

BACKGROUND: Limited data are available regarding the demographics, disease associations, and long-term prognosis of patients with inappropriate sinus tachycardia (IST). OBJECTIVE: To establish epidemiologic data for patients with IST, including symptom onset, comorbid disease, and long-term outcomes. METHODS: We retrospectively reviewed all patients with an IST diagnosis at the Mayo Clinic (Rochester, MN) during a 20-year period (1998-2018). We extracted demographic data and clinical outcomes compared to an age and gender-matched control group with atrioventricular nodal reentry tachycardia (AVNRT). RESULTS: Within the study period, a total of 305 patients with IST were identified (mean follow-up 3.5 years) with 92.1% female and mean age 33.2 ± 11.2 years. The most frequently identified circumstances triggering the condition included pregnancy (7.9%) and infectious illness (5.9%) while the most common comorbid conditions were depression (25.6%) and anxiety (24.6%). At diagnosis, the mean left ventricular ejection fraction (LVEF) was 62.3 ± 6.2%, with 77 patients having follow-up echocardiographic data. No significant difference in LVEF was seen after a mean 4.9 ± 4.3-year follow-up (baseline LVEF 59.8 ± 10.7% vs subsequent 61.4 ± 8.1%; P = .2971). Two deaths occurred within the study period, with one related to myocardial infarction and the other noncardiac; compared to an age and gender-matched AVNRT control group there was no excess mortality during the follow-up period. CONCLUSIONS: In our study cohort, IST predominately affects young females with structurally normal hearts and modest coexistent psychiatric disease. In most cases of IST, a major event occurring just before or at the time of diagnosis could not be identified, although nearly 8% of patients first noted symptoms during or shortly after pregnancy. In our cohort, there was no evidence of cardiomyopathy or mortality related to IST.

Association between the Charlson comorbidity index and outcomes after implantable cardioverter defibrillator generator replacement.

BACKGROUND: Recipients of implantable cardioverter defibrillator (ICD) generator replacement with multiple medical comorbidities may be at higher risk of adverse outcomes that attenuate the benefit of ICD replacement. The aim of this investigation was to study the association between the Charlson comorbidity index (CCI) and outcomes after ICD generator replacement. METHODS: All patients undergoing first ICD generator replacement at Mayo Clinic, Rochester and Beth Israel Deaconess Medical Center, Boston between 2001 and 2011 were identified. Outcomes included: (a) all-cause mortality, (b) appropriate ICD therapy, and (c) death prior to appropriate therapy. Multivariable Cox regression analysis was performed to assess association between CCI and outcomes. RESULTS: We identified 1421 patients with mean age of 69.6 ± 12.1 years, 81% male and median (range) CCI of 3 (0-18). During a mean follow-up of 3.9 ± 3 years, 52% of patients died, 30.6% experienced an appropriate therapy, and 23.6% died without experiencing an appropriate therapy. In multivariable analysis, higher CCI score was associated with increased all-cause mortality (Hazard ratio, HR 1.10 [1.06-1.13] per 1 point increase in CCI, P < .001), death without prior appropriate therapy (HR 1.11 [1.07-1.15], P < .0001), but not associated with appropriate therapy (HR 1.01 [0.97-1.05], P = .53). Patients with CCI ≥5 had an annual risk of death of 12.2% compared to 8.7% annual rate of appropriate therapy. CONCLUSIONS: CCI is predictive of mortality following ICD generator replacement. The benefit of ICD replacement in patients with CCI score ≥5 should be investigated in prospective studies.

Paced QRS morphology predicts incident left ventricular systolic dysfunction and atrial fibrillation.

BACKGROUND: The prognostic significance of paced QRS complex morphology on surface ECG remains unclear. This study aimed to assess long-term outcomes associated with variations in the paced QRS complex. METHODS: Adult patients who underwent dual-chamber pacemaker implantation with 20% or more ventricular pacing and a 12-lead ECG showing a paced complex were included. The paced QRS was analyzed in leads I and aVL. Long-term clinical and echocardiographic outcomes were compared at 5 years. RESULTS: The study included 844 patients (43.1% female; age 75.0 ±â€¯12.1). Patients with a longer paced QRS (pQRS) duration in lead I had a lower rate of atrial fibrillation (HR 0.80; p = 0.03) and higher rate of systolic dysfunction (HR 1.17; p < 0.001). Total pacing complex (TPC) duration was linked to higher rates of ICD implantation (HR 1.18; p = 0.04) and systolic dysfunction (HR 1.22, p < 0.001). Longer paced intrinsicoid deflection (pID) was associated with less atrial fibrillation (HR 0.75; p = 0.01), more systolic dysfunction (HR 1.17; p < 0.001), ICD implantation (HR 1.23; p = 0.04), and CRT upgrade (HR 1.23; p = 0.03). Exceeding thresholds for TPC, pQRS, and pID of 170, 146, and 112 ms in lead I, respectively, was associated with a substantial increase in systolic dysfunction over 5 years (p < 0.001). CONCLUSIONS: Longer durations of all tested parameters in lead I were associated with increased rates of left ventricular systolic dysfunction. ICD implantation and CRT upgrade were also linked to increased TPC and pID durations. Paradoxically, patients with longer pID and pQRS had less incident atrial fibrillation.

Right ventricular pacemaker lead position is associated with differences in long-term outcomes and complications.

INTRODUCTION: Cardiac pacing from the right ventricular apex is associated with detrimental long-term effects and nonapical pacing locations may be associated with improved outcomes. There is little data regarding complications with nonapical lead positions. The aim of this study was to assess long-term outcomes and lead-related complications associated with differing ventricular lead tip position. METHODS AND RESULTS: All adult patients who underwent dual-chamber pacemaker implantation from 2004 to 2014 were included if they had postprocedure chest radiographs amenable to lead position determination. Long-term outcomes and lead-related complication rates were recorded. These were compared at 5 years between: (1) apical and septal leads, (2) apical and nonseptal nonapical (NSNA), and (3) apical and septal with >40% ventricular pacing. We retrospectively evaluated 3,450 patients, which included 238 with a septal position and 733 with NSNA lead positions. Septal lead position was associated with a lower mortality compared to apical leads (24% vs. 31%, P = 0.02). In patients with greater than 40% pacing, septal leads were associated with significantly higher rates of incident atrial fibrillation compared to apical leads (49% vs. 34%, P = 0.04). NSNA positions were associated with a significantly higher rate of lead dislodgement (4% vs. 2%, P = 0.005) and need for revision (8% vs. 5%, P = 0.005). CONCLUSIONS: Septal pacemaker lead position is associated with a lower mortality compared to apically placed leads, but a higher incidence of atrial fibrillation with higher percentage ventricular pacing. NSNA lead locations are associated with more complications and should be avoided.

Denervation of the extrinsic cardiac sympathetic nervous system as a treatment modality for arrhythmia.

Denervation of the extrinsic cardiac sympathetic nervous system is a method of altering the autonomic tone experienced by the heart and vasculature. It has been studied and employed as a therapy for cardiac disease for decades. Currently, there is a high level of interest in using cardiac denervation for treatment of arrhythmias. This review describes the anatomy and physiology of the cardiac autonomic nervous system followed by a discussion of the mechanistic studies which provide a basis for the therapeutic use of sympathetic denervation. The clinical research supporting its use in human arrhythmias is then appraised, covering the standard indications, such as long QT syndrome, as well as future possibilities. Last, a detailed account of the methods for performing surgical cardiac denervation and percutaneous stellate ganglion anesthetic block is provided, including the complications of each procedure. An understanding of the anatomy and physiology of the cardiac autonomic nervous system along with the techniques of surgical denervation and percutaneous anesthetic block will allow the clinician to effectively discuss and implement these therapies.

Diagnosis of constrictive pericarditis obscured by hypertrophic cardiomyopathy: Back to basics.

In this report, we describe the case of a 41-year-old man with hypertrophic cardiomyopathy presenting with right-sided congestive heart failure symptoms. Noninvasive testing was suggestive, but non-diagnostic for constrictive pericarditis (CP) and thus invasive hemodynamic catheterization was performed. The unique presence of both hypertrophic cardiomyopathy and constriction in this case led to lack of "modern" echocardiographic and invasive criteria for CP, based upon findings of enhanced ventricular dependence. However, classic hemodynamic criteria of early rapid filling with elevation and end-equalization of diastolic pressures were present, and the patient ultimately received pericardiectomy with dramatic clinical improvement.

Left Bundle Branch Block: Current and Future Perspectives.

Left bundle branch block may be due to conduction system degeneration or a reflection of myocardial pathology. Left bundle branch block may also develop following aortic valve disease or cardiac procedures. Patients with heart failure with reduced ejection fraction and left bundle branch block may respond positively to cardiac resynchronization therapy. Lead placement via the coronary sinus is the mainstay approach of cardiac resynchronization therapy. However, other options, including physiological pacing, are being explored. In this review, we summarize the salient pathophysiologic and clinical aspects of left bundle branch block, as well as current and future strategies for management.

Cardiac Resynchronization Therapy in Preserved to Mildly Reduced Systolic Function.

Cardiac resynchronization therapy has been proven to be clearly beneficial for patients with heart failure, a prolonged QRS duration, and a left ventricular ejection fraction ≤35%. Ejection fraction cutoff, however, is arbitrary and very likely excludes many patients who could benefit from cardiac resynchronization. This article describes the major detrimental effects of left bundle branch block and summarizes the data regarding the potential beneficial effects of cardiac resynchronization in patients with a left ventricular ejection fraction greater than 35%.

Diagnostic Accuracy of Echocardiography and Intraoperative Surgical Inspection of the Unicuspid Aortic Valve.

Unicuspid aortic valve (UAV) is a rare malformation that is often difficult to distinguish from a bicuspid aortic valve (BAV) with commissural fusion by echocardiography or intraoperative surgical inspection. This study assessed the accuracy of intraoperative surgical inspection and two-dimensional echocardiography in diagnosing UAV compared to a gold standard of pathological diagnosis. The Mayo Clinic echocardiographic database, tissue registry database and electronic medical record were searched for all patients assigned a diagnosis of UAV by any technique. Transthoracic (TTE), transesophageal (TEE) echocardiographic, and surgical diagnoses were compared to pathological diagnosis as the standard. A clinical diagnosis of UAV was applied to 380 patients by 1 or more method and in 196 (52%) a pathologic evaluation was available to compare to the clinical description given by TTE, TEE, or surgical inspection. Of these 196 patients, only 58 (30%) had a pathological diagnosis of UAV; the majority were found to be BAVs by pathologic evaluation (n = 132, 67%). For diagnosing UAV, the sensitivity and specificity were 15% and 87% for TTE, 28%, and 82% for TEE, and 52% and 51% for surgical inspection, respectively. Valves with bicuspid morphology and extensive commissural fusion were frequently misclassified as UAV by all methods. In conclusion, intraoperative surgical inspection and echocardiography have limitations for diagnosing UAV due to difficulties in accurately assigning a correct morphological diagnosis, which suggests that the current understanding of the natural history of UAV may be inaccurate.

Three Cases of Rare Retroaortic Coronary Anomalies Diagnosed With Angiography and Cardiac CTA.

Coronary artery anomalies are relatively rare (approximately 1% on CTA). We present two exceedingly rare cases, as well as the first reported case of anomalous retro-aortic coronary arteries diagnosed with cardiac CTA and angiography.

Preprocedural Utility of the Echocardiographic Retroaortic Anomalous Coronary Sign.

Imaging series highlighting echocardiographic findings associated with the retroaortic anomalous coronary sign and its utility as a non-invasive modality to recognize technically complex and high-risk retroaortic coronary anomalies prior to intervention.

Intrapulmonary Vein Ablation Without Stenosis: A Novel Balloon-Based Direct Current Electroporation Approach.

BACKGROUND: Current thermal ablation methods for atrial fibrillation, including radiofrequency and cryoablation, have a suboptimal success rate. To avoid pulmonary vein (PV) stenosis, ablation is performed outside of the PV, despite the importance of triggers inside the vein. We previously reported on the acute effects of a novel direct current electroporation approach with a balloon catheter to create lesions inside the PVs in addition to the antrum. In this study, we aimed to determine whether the effects created by this nonthermal ablation method were associated with irreversible lesions and whether PV stenosis or other adverse effects occurred after a survival period. METHODS AND RESULTS: Initial and survival studies were performed in 5 canines. At the initial study, the balloon catheter was inflated to contact the antrum and interior of the PV. Direct current energy was delivered between 2 electrodes on the catheter in ECG-gated 100 µs pulses. A total of 10 PVs were treated demonstrating significant acute local electrogram diminution (mean amplitude decrease of 61.2±19.8%). After the survival period (mean 27 days), computed tomography imaging showed no PV stenosis. On histologic evaluation, transmural, although not circumferential, lesions were seen in each treated vein. No PV stenosis or esophageal injury was present. CONCLUSIONS: Irreversible, transmural lesions can be created inside the PV without evidence of stenosis after a 27-day survival period using this balloon-based direct current ablation approach. These early data show promise for an ablation approach that could directly treat PV triggers in addition to traditional PV antrum ablation.

Termination of Atrial Fibrillation With Epicardial Cooling in the Oblique Sinus.

OBJECTIVES: This study aimed to determine if epicardial cooling could repeatedly terminate induced atrial fibrillation (AF) in a canine heart. BACKGROUND: Rapid termination of AF could control symptoms and prevent atrial remodeling; however, defibrillation by internal electrical cardioversion is not tolerable to most patients. Cooling of the epicardium slows atrial conduction and may provide a less painful method to quickly terminate AF. METHODS: AF was induced with atrial myocardial epinephrine injections and rapid atrial pacing in an open-chest canine. Attempts at termination were performed with a small metal device that was either cooled to 5°C or kept at body temperature (control module). The device was placed on the epicardial surface in the oblique sinus. The time from device contact to termination of AF was recorded. RESULTS: In 5 different canine studies, there were 57 attempts at AF termination with either a 5°C module (34 attempts) or a control module (23 attempts). The median (interquartile range [IQR]) time to AF termination was 24 s (IQR: 15 to 35 s) for the 5°C therapy and 100 s (IQR: 47 to 240 s) for the body temperature treatments (p < 0.001). In the control group, there were 8 AF episodes that continued up to 4 min. Subsequent application of the 5°C cooling module terminated AF in all cases. CONCLUSIONS: Epicardial cooling in the oblique sinus is effective for repeated termination of AF in a canine heart. If reproduced in human studies, epicardial cooling with an implantable device may provide a method for management of patients with AF.

Risk of Appropriate Therapy and Death Before Therapy After Implantable Cardioverter-Defibrillator Generator Replacement.

Background The decision to initially implant an implantable cardioverter-defibrillator (ICD) is informed by robust randomized controlled trials, but no such data exist to guide the decision to replace an ICD generator. In this study, we aimed to determine outcomes after ICD generator replacement. Methods All patients with ischemic or nonischemic cardiomyopathy who underwent ICD generator replacement from 2001 to 2011 at Mayo Clinic, MN, or Beth Israel Deaconess Medical Center, MA, were included. Outcomes included (1) appropriate therapy after generator replacement and (2) death before appropriate therapy after generator replacement. Cox proportional hazards modeling was used to determine the associations between patient characteristics and outcomes. Results In 1421 patients undergoing ICD generator replacement (mean±SD age 69.6±12.1 years, 81% male), appropriate therapy occurred after replacement in 435 patients (30.6%) over a mean follow-up of 2.7±2.6 years. Associated factors included lower left ventricular ejection fraction and history of appropriate therapy before generator replacement. Death before appropriate ICD therapy occurred in 336 (23.7%) patients. Older age, lower left ventricular ejection fraction, and noncardiac comorbidities, including diabetes mellitus, chronic lung disease, peripheral vascular disease, lower hemoglobin, and lower glomerular filtration rate, were associated with greater risk of death before appropriate therapy. A progressive increase in mortality was observed with aggregation of these noncardiac comorbidities. Conclusions The decision to replace the ICD should take into consideration not only left ventricular ejection fraction and history of ventricular arrhythmias, but also comorbid illnesses that may impact the duration and the quality of life.

The maverick heart sound.

CLINICAL INTRODUCTION: An asymptomatic 29-year-old woman presented for prenatal counselling. She had a history of a heart murmur since childhood and a previous echocardiogram suggesting 'enlargement of the heart'. Physical exam revealed normal jugular venous pressure and contour. Precordial palpation was unremarkable. Auscultation, however, was abnormal; findings on inspiration and expiration are presented in Figure 1, sound clip. QUESTION: Based on the phonocardiogram and online supplementary audio clip, which of the following is correct? An early diastolic filling sound (S3) is heard, indicating increased right ventricular filling pressures.An ejection click without respiratory variation and a systolic ejection murmur are heard, consistent with bicuspid aortic valve stenosis.An ejection click with respiratory variation and a systolic ejection murmur are heard, consistent with pulmonic valve stenosis.A holosystolic murmur with inspiratory augmentation is heard, indicating tricuspid regurgitation.

Outcomes With Left Bundle Branch Block and Mildly to Moderately Reduced Left Ventricular Function.

OBJECTIVES: This study aimed to define the prognosis for patients with left bundle branch block (LBBB) and a mildly to moderately reduced left ventricular ejection fraction (LVEF) (36% to 50%) as well as to clarify whether LBBB remained a negative prognostic marker in this group. BACKGROUND: LBBB is associated with worse outcomes in patients with heart failure in the setting of severely reduced LVEF. The level of morbidity and mortality associated with LBBB in the setting of a mildly to moderately reduced LVEF (36% to 50%) has not been clearly characterized. This knowledge is important to clarify the potential benefit of cardiac resynchronization therapy in this group. METHODS: All patients identified as having an LBBB from 1994 to 2014 were included in the study if they had a baseline echocardiogram within 1 year and an LVEF between 36% and 50%. A control group without intraventricular conduction abnormality matched on age, sex, baseline LVEF, and date of echocardiogram was created. Outcomes were compared between the 2 groups. RESULTS: Of 1,436 patients meeting inclusion criteria, 54% were male. Mean age was 67 ± 13 years, and mean LVEF at baseline was 44 ± 4%. There was no difference in baseline heart failure diagnosis between groups. There were significantly higher rates of baseline coronary artery disease in the control group and higher rates of aortic stenosis in the LBBB group. LBBB was associated with significantly worse mortality (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.00 to 1.36), an LVEF drop to 35% or less (HR: 1.34; 95% CI: 1.09 to 1.63), and the need for an implantable cardioverter-defibrillator (HR: 1.50; 95% CI: 1.10 to 2.10). Mortality remained significantly higher in the LBBB group when controlled for heart failure, coronary artery disease, and aortic stenosis (p = 0.04). CONCLUSIONS: Patients with a mildly to moderately reduced LVEF and LBBB have poor clinical outcomes that are significantly worse than those for patients without conduction system disease. This group may obtain benefit from cardiac resynchronization therapy and deserves to be studied in prospective trials.

Outcomes After Implantable Cardioverter-Defibrillator Generator Replacement for Primary Prevention of Sudden Cardiac Death.

BACKGROUND: The effectiveness of implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden death in patients with an ejection fraction (EF) ≤ 35% and clinical heart failure is well established. However, outcomes after replacement of the ICD generator in patients with recovery of EF to >35% and no previous therapies are not well characterized. METHODS AND RESULTS: Between 2001 and 2011, generator replacement was performed at 2 tertiary medical centers in 253 patients (mean age, 68.3 ± 12.7 years; 82% men) who had previously undergone ICD placement for primary prevention but subsequently never received appropriate ICD therapy. EF had recovered to > 35% in 72 of 253 (28%) patients at generator replacement. During median (quartiles) follow-up of 3.3 (1.8-5.3) years after generator replacement, 68 of 253 (27%) experienced appropriate ICD therapy. Patients with EF ≤ 35% were more likely to experience ICD therapy compared with those with EF > 35% (12% versus 5% per year; hazard ratio, 3.57; P = 0.001). On multivariable analysis, low EF predicted appropriate ICD therapy after generator replacement (hazard ratio, 1.96 [1.35-2.87] per 10% decrement; P = 0.001). Death occurred in 25% of patients 5 years after generator replacement. Mortality was similar in patients with EF ≤ 35% and > 35% (7% versus 5% per year; hazard ratio, 1.10; P = 0.68). Atrial fibrillation (3.24 [1.63-6.43]; P < 0.001) and higher blood urea nitrogen (1.28 [1.14-1.45] per increase of 10 mg/dL; P < 0.001) were associated with mortality. CONCLUSIONS: Although approximately one fourth of patients with a primary prevention ICD and no previous therapy have EF >35% at the time of generator replacement, these patients continue to be at significant risk for appropriate ICD therapy (5% per year). These data may inform decisions on ICD replacement.