Advancing Cardiovascular Risk Assessment with Artificial Intelligence: Opportunities and Implications in North Carolina.

Cardiovascular disease mortality is increasing in North Carolina with persistent inequality by race, income, and location. Artificial intelligence (AI) can repurpose the widely available electrocardiogram (ECG) for enhanced assessment of cardiac dysfunction. By identifying accelerated cardiac aging from the ECG, AI offers novel insights into risk assessment and prevention.

Prevalence and Predictors of Mitral Annular Disjunction and Ventricular Ectopy in Mitral Valve Prolapse.

BACKGROUND: Mitral annular disjunction (MAD) is associated with ventricular arrhythmia in mitral valve prolapse (MVP). The proportional risk from MAD and other predictors of ventricular arrhythmia in MVP have not been well characterized. OBJECTIVE: To identify predictors of complex or frequent ventricular ectopy (cfVE) in MVP and quantify risk of cfVE and mortality in MVP with MAD. METHODS: We studied 632 adult patients with MVP on transthoracic echocardiography at the University of North Carolina Medical Center from 2016-2019 (median age [IQR] 64 [52-74] years; 52.7% female; 16.3% African American). Resting and ambulatory electrocardiograms were used to identify cfVE. RESULTS: MAD was present in 94 (14.9%) patients. Independent associations of MAD were bileaflet prolapse (OR [95% CI] 4.25 [2.47-7.33], p<0.0001), myxomatous valve (2.17 [1.27-3.71], p=0.005), absence of hypertension (2.00 [1.21-3.32], p=0.007), electrocardiogram inferior or lateral lead T-wave inversion (TWI, 2.07 [1.23-3.48], p=0.006), and female sex (1.99 [1.21-3.25], p=0.006). cfVE was frequent with MAD (39 [41.5%] vs 93 [17.3%] without, p<0.0001). Independent cfVE predictors were MAD (HR [95% CI] 2.23 [1.47-3.36], p=0.0001), bileaflet prolapse (1.86 [1.25-2.76], p=0.002), heart failure (1.79 [1.16-2.77], p=0.009), lower LV ejection fraction (0.14 [0.03-0.61], p=0.009), coronary artery disease (1.60 [1.05-2.43], p=0.03), and TWI (1.51 [1.03-2.22], p=0.03). After median 40 (33-48) months, there was increased mortality with MAD (p=0.04). CONCLUSION: MAD in MVP is associated with bileaflet or myxomatous MVP, absence of hypertension, T-wave inversion, and female sex. There is increased complex and frequent ventricular ectopy and mortality with MAD, highlighting the need for closer follow-up in these patients.

Developing a Mechanistic Approach to Sudden Death Prevention in Mitral Valve Prolapse.

Sudden cardiac death (SCD) from ventricular fibrillation (VF) can occur in mitral valve prolapse (MVP) in the absence of other comorbidities including mitral regurgitation, heart failure or coronary disease. Although only a small proportion with MVP are at risk, it can affect young, otherwise healthy adults, most commonly premenopausal women, often as the first presentation of MVP. In this review, we discuss arrhythmic mechanisms in MVP and mechanistic approaches for sudden death risk assessment and prevention. We define arrhythmogenic or arrhythmic MVP (AMVP) as MVP associated with complex and frequent ventricular ectopy, and malignant MVP (MMVP) as MVP with high risk of SCD. Factors predisposing to AMVP are myxomatous, bileaflet MVP and mitral annular disjunction (MAD). Data from autopsy, cardiac imaging and electrophysiological studies suggest that ectopy in AMVP is due to inflammation, fibrosis and scarring within the left ventricular (LV) base, LV papillary muscles and Purkinje tissue. Postulated mechanisms include repetitive injury to these regions from systolic papillary muscle stretch and abrupt mitral annular dysmotility (excursion and curling) and diastolic endocardial interaction of redundant mitral leaflets and chordae. Whereas AMVP is seen relatively commonly (up to 30%) in those with MVP, MVP-related SCD is rare (2-4%). However, the proportion at risk (i.e., with MMVP) is unknown. The clustering of cardiac morphological and electrophysiological characteristics similar to AMVP in otherwise idiopathic SCD suggests that MMVP arises when specific arrhythmia modulators allow for VF initiation and perpetuation through action potential prolongation, repolarization heterogeneity and Purkinje triggering. Adequately powered prospective studies are needed to assess strategies for identifying MMVP and the primary prevention of SCD, including ICD implantation, sympathetic modulation and early surgical mitral valve repair. Given the low event rate, a collaborative multicenter approach is essential.

Feasibility of directional percutaneous epicardial ablation with a partially insulated catheter.

PURPOSE: To demonstrate the feasibility of directional percutaneous epicardial ablation using a partially insulated catheter. METHODS: Partially insulated catheter prototypes were tested in 12 (6 canine, 6 porcine) animal studies in two centers. Prototypes had interspersed windows to enable visualization of epicardial structures with ultrasound. Epicardial unipolar ablation and ablation between two electrodes was performed according to protocol (5-60 W power, 0-60 mls/min irrigation, 78 s mean duration). RESULTS: Of 96 epicardial ablation attempts, unipolar ablation was delivered in 53.1%. Electrogram evidence of ablation, when analyzable, occurred in 75 of 79 (94.9%) therapies. Paired pre/post-ablation pacing threshold (N = 74) showed significant increase in pacing threshold post-ablation (0.9 to 2.6 mA, P < .0001). Arrhythmias occurred in 18 (18.8%) therapies (11 ventricular fibrillation, 7 ventricular tachycardia), mainly in pigs (72.2%). Coronary artery visualization was variably successful. No phrenic nerve injury was noted during or after ablation. Furthermore, there were minimal pericardial changes with ablation. CONCLUSIONS: Epicardial ablation using a partially insulated catheter to confer epicardial directionality and protect the phrenic nerve seems feasible. Iterations with ultrasound windows may enable real-time epicardial surface visualization thus identifying coronary arteries at ablation sites. Further improvements, however, are necessary.

Effusive-Constrictive Pericarditis After Pericardiocentesis: Incidence, Associated Findings, and Natural History.

OBJECTIVES: This study sought to investigate the incidence, associated findings, and natural history of effusive-constrictive pericarditis (ECP) after pericardiocentesis. BACKGROUND: ECP is characterized by the coexistence of tense pericardial effusion and constriction of the heart by the visceral pericardium. Echocardiography is currently the main diagnostic tool in the assessment of pericardial disease, but limited data have been published on the incidence and prognosis of ECP diagnosed by echo-Doppler. METHODS: A total of 205 consecutive patients undergoing pericardiocentesis at Mayo Clinic, Rochester, Minnesota, were divided into 2 groups (ECP and non-ECP) based on the presence or absence of post-centesis echocardiographic findings of constrictive pericarditis. Clinical, laboratory, and imaging characteristics were compared. RESULTS: ECP was subsequently diagnosed in 33 patients (16%) after pericardiocentesis. Overt clinical cardiac tamponade was present in 52% of ECP patients and 36% of non-ECP patients (p = 0.08). Post-procedure hemopericardium was more frequent in the ECP group (33% vs. 13%; p = 0.003), and a higher percentage of neutrophils and lower percentage of monocytes were noted on pericardial fluid analysis in those patients. Clinical and laboratory findings were otherwise similar. Baseline early diastolic mitral septal annular velocity was significantly higher in the ECP group. Before pericardiocentesis, respiratory variation of mitral inflow velocity, expiratory diastolic flow reversal of hepatic vein, and respirophasic septal shift were significantly more frequent in the ECP group. Fibrinous or loculated effusions were also more frequently observed in the ECP group. Four deaths occurred in the ECP group; all 4 patients had known malignancies. During median follow-up of 3.8 years (interquartile range: 0.5 to 8.3 years), only 2 patients required pericardiectomy for persistent constrictive features and symptoms. CONCLUSIONS: In a large cohort of unselected patients undergoing pericardiocentesis, 16% were found to have ECP. Pre-centesis echocardiographic findings might identify such patients. Long-term prognosis in those patients remains good, and pericardiectomy was rarely required.

A Novel Defibrillation Tool: Percutaneously Delivered, Partially Insulated Epicardial Defibrillation.

INTRODUCTION: Epicardial defibrillation systems currently require surgical access. We aimed to develop a percutaneous defibrillation system with partially-insulated epicardial coils to focus electrical energy on the myocardium and prevent or minimize extra-cardiac stimulation. METHODS: We tested 2 prototypes created for percutaneous introduction into the pericardial space via a steerable sheath. This included a partially-insulated defibrillation coil and a defibrillation mesh with a urethane balloon acting as an insulator to the face of the mesh not in contact with the epicardium. The average energy associated with a chance of successful defibrillation 75% of the time (ED75) was calculated for each experiment. RESULTS: Of 16 animal experiments, 3 pig experiments had malfunctioning mesh prototypes such that results were unreliable; these were excluded. Therefore, 13 animal experiments were analyzed - 6 canines (29.8±4.0kg); 7 pigs (41.1±4.4kg). The overall ED75 was 12.8±6.7J (10.9±9.1J for canines; 14.4±3.9J in pigs [P=0.37]). The lowest ED75 obtained in canines was 2.5J while in pigs it was 9.5J. The lowest energy resulting in successful defibrillation was 2J in canines and 5J in pigs. There was no evidence of coronary vessel injury or trauma to extra-pericardial structures. CONCLUSION: Percutaneous, epicardial defibrillation using a partially insulated coil is feasible and appears to be associated with low defibrillation thresholds. Focusing insulation may limit extra-cardiac stimulation and potentially lower energy requirements for efficient defibrillation.

Sites of Successful Ventricular Fibrillation Ablation in Bileaflet Mitral Valve Prolapse Syndrome.

BACKGROUND: Although the vast majority of mitral valve prolapse (MVP) is benign, a small subset of patients, predominantly women, with bileaflet prolapse, complex ventricular ectopy (VE), and abnormal T waves comprise the recently described bileaflet MVP syndrome. We compared findings on electrophysiological study in bileaflet MVP syndrome patients with and without cardiac arrest to identify factors that may predispose to malignant ventricular arrhythmia. METHODS AND RESULTS: Fourteen consecutive bileaflet MVP syndrome patients (n=13 women; median [limits], age at index ablation, 33.8 [21.0-58.7] years; ejection fraction, 60% [45%-67%]; all ≤ moderate mitral regurgitation; n=6 with previous cardiac arrest and implantable cardioverter defibrillator shocks for ventricular fibrillation; and n=8 without implantable cardioverter defibrillator although with symptomatic complex VE) were included. The 2 groups had similar baseline echocardiographic and electrocardiographic characteristics. All patients had at least 1 left ventricular papillary or fascicular VE focus. Purkinje origin VE was identified as the ventricular fibrillation trigger in 6 of 6 cardiac arrest patients (4 from papillary muscle) and Purkinje origin of dominant VE was seen in 5 of 8 (3 from papillary muscle) nonarrest patients. Acute success was seen in 17 of 19 procedures, and a ventricular fibrillation storm occurred within 24 hours of ablation in a single patient. Repeat ablation for recurrent symptomatic arrhythmia was performed in 6 patients. At 478 (39-2099) days of follow-up, 2 cardiac arrest patients received appropriate shocks. Symptoms from VE were reduced in 12 of 14. CONCLUSIONS: Bileaflet MVP syndrome is characterized by fascicular and papillary muscle VE that triggers ventricular fibrillation. Ablation of clinically dominant VE foci improves symptoms and reduces appropriate implantable cardioverter defibrillator shocks.

Left Atrial Appendage Exclusion for Atrial Fibrillation.

Percutaneous left atrial appendage (LAA) closure is being increasingly used as a treatment strategy to prevent stroke in patients with atrial fibrillation (AF) who have contraindications to anticoagulants. Several approaches and devices have been developed in the last few years, each with their own unique set of advantages and disadvantages. In this article, the published studies on surgical and percutaneous approaches to LAA closure are reviewed, focusing on stroke mechanisms in AF, LAA structure and function relevant to stroke prevention, practical differences in procedural approach, and clinical considerations surrounding management.

Reduction in malignant ventricular arrhythmia and appropriate shocks following surgical correction of bileaflet mitral valve prolapse.

BACKGROUND: Bileaflet mitral valve prolapse (MVP) can be associated with malignant ventricular arrhythmias. It is unknown whether surgical correction alone of this mitral valve pathology leads to a reduction in ventricular dysrhythmias. METHODS: We retrospectively analyzed 4477 patients who underwent mitral valve surgery from 1993-2013 at Mayo Clinic in Rochester, MN. Among these, eight patients with bileaflet MVP who had an internal cardioverter defibrillator (ICD) in place both pre- and post-surgery were identified. ICD interrogation records were evaluated for episodes of ventricular tachycardia (VT), ventricular fibrillation (VF), and appropriate ICD shock therapy. RESULTS: Of these eight patients, five had a malignant ventricular arrhythmia prior to surgery. Data was available 4.6 ± 2.9 years before versus 6.6 ± 4.2 years following surgical intervention. Among these patients, there was a reduction in VF (0.6 versus 0.14 events per-person-year pre- and post-surgery, respectively), VT (0.4 versus 0.05 events per-person-year pre- and post-surgery, respectively), and ICD shocks (0.95 versus 0.19 events per-person-year pre- and post-surgery) following mitral valve surgery. CONCLUSIONS: We report a series of cases where the surgical correction of bileaflet MVP alone was associated with a reduction in malignant arrhythmia and appropriate shocks. These early observations merit further investigation involving larger cohorts to further evaluate the association between abnormal mechanical forces in degenerative mitral valve disease and ventricular dysrhythmias.

The effect of mitral valve surgery on ventricular arrhythmia in patients with bileaflet mitral valve prolapse.

BACKGROUND: Bileaflet mitral valve prolapse (biMVP) is associated with frequent ventricular ectopy (VE) and malignant ventricular arrhythmia. We examined the effect of mitral valve (MV) surgery on VE burden in biMVP patients. METHODS: We included 32 consecutive patients undergoing MV surgery for mitral regurgitation secondary to biMVP between 1993 and 2012 at Mayo Clinic who had available pre- and post-operative Holter monitoring data. Characteristics of patients with a significant reduction in postoperative VE (group A, defined as >10% reduction in VE burden compared to baseline) were compared with the rest of study patients (group B). RESULTS: In the overall cohort, VE burden was unchanged after the surgery (41 interquartile range [16, 196] pre-surgery vs. 40 interquartile range [5186] beats/hour [bph] post-surgery; P = 0.34). However, in 17 patients (53.1%), VE burden decreased by at least 10% after the surgery. These patients (group A) were younger than the group B (59 ± 15 vs. 68 ± 7 years; P = 0.04). Other characteristics including pre- and postoperative left ventricular function and size were similar in both groups. Age <60 years was associated with a reduction in postoperative VE (odds ratio 5.8; 95% confidence interval, 1.1-44.7; P = 0.03). Furthermore, there was a graded relationship between age and odds of VE reduction with surgery (odds ratio 1.9; 95% confidence interval 1.04-4.3 per 10-year; P = 0.04). CONCLUSIONS: MV surgery does not uniformly reduce VE burden in patients with biMVP. However, those patients who do have a reduction in VE burden are younger, perhaps suggesting that early surgical intervention could modify the underlying electrophysiologic substrate.

Direct Pulmonary Vein Ablation With Stenosis Prevention Therapy.

INTRODUCTION: The dominant location of electrical triggers for initiating atrial fibrillation (AF) originates from the muscle sleeves inside pulmonary veins (PVs). Currently, radiofrequency ablation (RFA) is performed outside of the PVs to isolate, rather than directly ablate these tissues, due to the risk of intraluminal PV stenosis. METHODS: In 4 chronic canine experiments, we performed direct PV muscle sleeve RFA ± postablation drug-coated balloon (DCB) treatment with paclitaxel/everolimus. Of the 4 PVs, 2 PVs were ablated and treated with DCB, 1 PV was ablated without DCB treatment (positive control), and 1 PV was left as a negative control. Local electrograms were assessed in PVs for near-field signals and were targeted for ablation. After 12-14 weeks survival, PVs were interrogated for absence of near-field PV potentials, and each PV was assessed for stenosis. RESULTS: All canines survived the study period without cardiorespiratory complications, and remained ambulatory. In all canines, PVs that were ablated and treated with DCB remained without any significant intraluminal stenosis. In contrast, PVs that were ablated and not treated with DCB showed near or complete intraluminal stenosis. At terminal study, PV potentials remained undetectable. A blinded, histologic analysis demonstrated that ablated PVs without DCB treatment had extensive thrombus, fibrin, mineralization, and elastin disruption. CONCLUSION: Our chronic canine data suggest that direct PV tissue ablation without subsequent stenosis is feasible with the use of postablation DCBs.

Mechanistic insights into transient severe mitral regurgitation.

Acute mitral regurgitation (AMR), a known complication of acute coronary syndromes, is usually associated with posterior papillary muscle dysfunction/rupture. In severe cases, management of AMR requires surgical intervention. Reversible severe AMR in patients in the absence of left ventricular systolic dysfunction and coronary artery stenosis may result from processes which cause transient subendocardial ischemia, such as intermittent episodes of hypotension or coronary artery vasospasm. We present two cases of reversible transient AMR due to subendocardial and/or endocardial ischemia, both of which offer insight into the mechanism of transient severe AMR.

Percutaneous Epicardial Pacing using a Novel Insulated Multi-electrode Lead.

INTRODUCTION: Epicardial cardiac resynchronization therapy (CRT) permits unrestricted electrode positioning. However, this requires surgical placement of device leads and the risk of unwanted phrenic nerve stimulation. We hypothesized that shielded electrodes can capture myocardium without extracardiac stimulation. METHODS: In 6 dog and 5 swine experiments, we used a percutaneous approach to access the epicardial surface of the heart, and deploy novel leads housing multiple electrodes with selective insulation. Bipolar pacing thresholds at prespecified sites were tested compare electrode threshold data both facing towards and away from the epicardial surface. RESULTS: In 151 paired electrode recordings (70 in 6 dogs; 81 in 5 swine), thresholds facing myocardium were lower than facing away (median [IQR] mA: dogs 0.9 [0.4-1.6] vs 4.6 [2.1 to >10], p<0.0001; swine 0.5 [0.2-1] vs 2.5 [0.5-6.8], p<0.0001). Myocardial capture was feasible without extracardiac stimulation at all tested sites, with mean ± SE threshold margin 3.6±0.7 mA at sites of high output extracardiac stimulation (p=0.004). CONCLUSION: Selective electrode insulation confers directional pacing to a multielectrode epicardial pacing lead. This device has the potential for a novel percutaneous epicardial resynchronization therapy that permits placement at an optimal pacing site, irrespective of the anatomy of the coronary veins or phrenic nerves.

Optimization Of Stroke Prophylaxis Strategies In Nonvalvular AF -Drugs, Devices Or Both?

Atrial fibrillation (AF) is the most common cardiac arrhythmia with the prevalence increasing over time. AF probably afflicts ≥2% of worldwide adult population and increases with age.[1-3] In the Framingham Heart Study, the lifetime risk of having at least one episode of AF for 40-year-old men and women was 26% and 23% respectively.[4].