Christopher D. Nielsen

Alcohol Septal Ablation for the Treatment of Hypertrophic Obstructive Cardiomyopathy: A Multicenter North American Registry

OBJECTIVES The purpose of the study is to identify the predictors of clinical outcome (mortality and survival without repeat septal reduction procedures) of alcohol septal ablation for the treatment of patients with hypertrophic obstructive cardiomyopathy. BACKGROUND Alcohol septal ablation is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe outflow tract obstruction. The existing literature is limited to single-center results, and predictors of clinical outcome after ablation have not been determined. Registry results can add important data. METHODS Hypertrophic obstructive cardiomyopathy patients (N = 874) who underwent alcohol septal ablation were enrolled. The majority (64%) had severe obstruction at rest, and the remaining had provocable obstruction. Before ablation, patients had severe dyspnea (New York Heart Association [NYHA] functional class III or IV: 78%) and/or severe angina (Canadian Cardiovascular Society angina class III or IV: 43%). RESULTS Significant improvement (p < 0.01) occurred after ablation (~5% in NYHA functional classes III and IV, and 8 patients in Canadian Cardiovascular Society angina class III). There were 81 deaths, and survival estimates at 1, 5, and 9 years were 97%, 86%, and 74%, respectively. Left anterior descending artery dissections occurred in 8 patients and arrhythmias in 133 patients. A lower ejection fraction at baseline, a smaller number of septal arteries injected with ethanol, a larger number of ablation procedures per patient, a higher septal thickness post-ablation, and the use beta-blockers post-ablation predicted mortality. CONCLUSIONS Variables that predict mortality after ablation, include baseline ejection fraction and NYHA functional class, the number of septal arteries injected with ethanol, post-ablation septal thickness, beta-blocker use, and the number of ablation procedures.

Follow-up of alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy the Baylor and Medical University of South Carolina experience 1996 to 2007.

OBJECTIVES This study sought to determine the long-term outcome of alcohol septal ablation (ASA). BACKGROUND There are inadequate data on the long-term outcome of ASA for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). METHODS Six hundred and twenty-nine patients were enrolled consecutively (1996 to 2007) and 98.4% (n = 619) underwent ASA with 92% follow-up in 2007. Evaluation included deaths, procedural complications, pacemaker requirement, repeat ASA, and myectomy/valve surgery. Follow-up parameters included angina (Canadian Cardiovascular Society score), dyspnea (New York Heart Association functional class), exercise time, and echocardiographic indices (septal thickness, ejection fraction, resting and provoked gradients). RESULTS Ethanol (2.6 +/- 1.0 ml) was injected into 1.3 +/- 0.5 septal arteries, inducing a septal infarct. Complications included death 1% (n = 6), permanent pacemaker requirement 8.2% (n = 52), coronary dissection 1.3% (n = 8), and worsening mitral regurgitation 0.3% (n = 2). The mean follow-up was 4.6 +/- 2.5 years (range: 3 months to 10.2 years). During follow-up, New York Heart Association functional class decreased from 2.8 +/- 0.6 to 1.2 +/- 0.5 (p < 0.001); Canadian Cardiovascular Society angina score decreased from 2.1 +/- 0.9 to 1.0 +/- 0 (p < 0.001); and exercise time increased from 4.8 +/- 3.3 to 8.2 +/- 1.0 (p < 0.001) min. The resting and provoked left ventricular outflow tract gradients decreased progressively (p < 0.001) and remained low during follow-up. The septal thickness decreased from 2.1 +/- 0.5 cm to 1.0 +/- 0.1 cm (p < 0.001) and the ejection fraction decreased from 68 +/- 9% to 62 +/- 3% (p < 0.001). The survival estimates at 1, 5, and 8 years were 97%, 92%, and 89%, respectively. CONCLUSIONS The initial benefits of ASA were maintained during follow-up.

Implantable Cardioverter-Defibrillator Therapy for Primary Prevention of Sudden Death After Alcohol Septal Ablation of Hypertrophic Cardiomyopathy

OBJECTIVES The purpose of this study was to examine the effects of alcohol septal ablation (ASA) on ventricular arrhythmias among patients with obstructive hypertrophic cardiomyopathy (HCM), as measured by appropriate implantable cardioverter-defibrillator (ICD) discharges. BACKGROUND Alcohol septal ablation is an effective therapy for patients with symptomatic HCM. However, concern has been raised that ASA may be proarrhythmic secondary to the iatrogenic scar created during the procedure. The impact of ASA on ventricular arrhythmias has not been well described. METHODS This prospective study included 123 consecutive patients with obstructive HCM who underwent ASA and had an ICD implanted for primary prevention of sudden cardiac death (SCD). The ICDs were implanted based on commonly accepted risk factors for SCD in the HCM population. Data from ICD interrogations during routine follow-up were collected. RESULTS Nine appropriate ICD shocks were recorded over a mean follow-up of 2.9 years in the cohort, which had a mean of 1.5 +/- 0.9 risk factors for SCD. Using Kaplan-Meier survival analysis, the estimated annual event rate was 2.8% over 3-year follow-up. There were no significant differences in the incidence of risk factors between patients who did and did not receive appropriate shocks. CONCLUSIONS The annual rate of appropriate ICD discharges after ASA is low and less than that reported previously for primary prevention of SCD in HCM. This suggests that ASA is not proarrhythmic. Traditional SCD risk factors did not predict ICD shocks in this cohort.

Electrocardiographic Findings After Alcohol Septal Ablation Therapy for Obstructive Hypertrophic Cardiomyopathy

Ablation of the septal myocardium with alcohol in patients with obstructive hypertrophic cardiomyopathy has been shown to improve symptoms, reduce ventricular outflow gradients, and improve cardiac function. 1,2 Acute electrocardiographic changes in a small group of patients have been reported. 3,4 Later changes have not been evaluated. This study presents 165 patients who underwent ablation therapy and preand post-procedure electrocardiography. ••• One hundred sixty-five consecutive patients treated for symptomatic obstructive hypertrophic cardiomyopathy with alcohol septal reduction therapy underwent pre- and post-procedure electrocardiography. All patients had symptoms refractory to medical therapy and resting gradients of 40 mm Hg or a dobutamineprovoked gradient 60 mm Hg using 5 to 20 g/kg/ min of dobutamine. Almost all patients were classified as having New York Heart Association class III or IV symptoms before the procedure. More details of the procedure have been reported in an earlier publication. 5 Resting 12-lead electrocardiograms were obtained before the procedure and then 2 to 286 days after ablation therapy. All electrocardiograms were reviewed independent of outcomes by 2 observers. Electrocardiograms were reviewed for Q waves, repolarization abnormalities, conduction abnormalities, QRS morphology, arrhythmias, left atrial enlargement, and left ventricular hypertrophy. Romhilt-Estes point system criteria were used to diagnose left ventricular hypertrophy. 6 The median follow-up period was 3 months (mean 60 days). Of the initial 190 patients, 25 (13%) had paced rhythms from prior placed pacemakers as a method of treatment for hypertrophic cardiomyopathy (which was unsuccessful) and were excluded from the study. The most common finding at baseline in the remaining 165 patients (Figure 1) was left ventricular hypertrophy (82 patients, 50%). Left atrial enlargement was also seen in 67 patients (41%) at baseline. Forty-nine patients (30%) were found to have significant Q waves at baseline. Most Q waves (30 of 49, 61%) were found in the septal precordial leads. Atrial fibrillation or atrial flutter was found in 8 patients (5%) before alcohol ablation. The most common conduction abnormality was left anterior fasicular block (17 patients, 10%). Six patients (4%) had right bundle branch block and 6 (4%) had left bundle branch block. First-degree atrioventricular block was noted in 9 patients (6%).

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A Phase 2, Randomized, Sham-Controlled Trial

Background: In nonrandomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), fewer symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and midrange or preserved ejection fraction (EF ≥40%). We conducted the first randomized sham-controlled trial to evaluate the IASD in HF with EF ≥40%. Methods: REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association class III or ambulatory class IV HF, EF ≥40%, exercise PCWP ≥25 mm Hg, and PCWP-right atrial pressure gradient ≥5 mm Hg. Participants were randomized (1:1) to the IASD versus a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness end point was exercise PCWP at 1 month. The primary safety end point was major adverse cardiac, cerebrovascular, and renal events at 1 month. PCWP during exercise was compared between treatment groups using a mixed-effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results: A total of 94 patients were enrolled, of whom 44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years, and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared with sham control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mm Hg in the treatment group versus 0.5±5.0 mm Hg in the control group (P=0.14). There were no peri-procedural or 1-month major adverse cardiac, cerebrovascular, and renal events in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). Conclusions: In patients with HF and EF ≥40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02600234.

Left ventricular end-diastolic pressure affects measurement of fractional flow reserve

BACKGROUND Fractional flow reserve (FFR), the hyperemic ratio of distal (Pd) to proximal (Pa) coronary pressure, is used to identify the need for coronary revascularization. Changes in left ventricular end-diastolic pressure (LVEDP) might affect measurements of FFR. METHODS AND MATERIALS LVEDP was recorded simultaneously with Pd and Pa during conventional FFR measurement as well as during additional infusion of nitroprusside. The relationship between LVEDP, Pa, and FFR was assessed using linear mixed models. RESULTS Prospectively collected data for 528 cardiac cycles from 20 coronary arteries in 17 patients were analyzed. Baseline median Pa, Pd, FFR, and LVEDP were 73 mmHg, 49 mmHg, 0.69, and 18 mmHg, respectively. FFR<0.80 was present in 14 arteries (70%). With nitroprusside median Pa, Pd, FFR, and LVEDP were 61 mmHg, 42 mmHg, 0.68, and 12 mmHg, respectively. In a multivariable model for the entire population LVEDP was positively associated with FFR such that FFR increased by 0.008 for every 1-mmHg increase in LVEDP (beta=0.008; P<0.001), an association that was greater in obstructed arteries with FFR<0.80 (beta=0.01; P<0.001). Pa did not directly affect FFR in the multivariable model, but an interaction between LVEDP and Pa determined that LVEDPs effect on FFR is greater at lower Pa. CONCLUSIONS LVEDP was positively associated with FFR. The association was greater in obstructive disease (FFR<0.80) and at lower Pa. These findings have implications for the use of FFR to guide revascularization in patients with heart failure. SUMMARY FOR ANNOTATED TABLE OF CONTENTS The impact of left ventricular diastolic pressure on measurement of fractional flow reserve (FFR) is not well described. We present a hemodynamic study of the issue, concluding that increasing left ventricular diastolic pressure can increase measurements of FFR, particularly in patients with FFR<0.80 and lower blood pressure.

Alcohol septal ablation for obstructive hypertrophic cardiomyopathy: Outcomes in young, middle-aged, and elderly patients

We compared the efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) in young, middle‐aged, and elderly patients.

Comparison of percutaneous coronary intervention safety before and during the establishment of a transradial program at a teaching hospital.

This study sought to examine the safety of percutaneous coronary intervention (PCI) before and during de novo establishment of a transradial (TR) program at a teaching hospital. TR access remains underused in the United States, where cardiology fellowship programs continue to produce cardiologists with little TR experience. Establishment of TR programs at teaching hospitals may affect PCI safety. Starting in July 2009 a TR program was established at a teaching hospital. PCI-related data for academic years 2008 to 2009 (Y1) and 2009 to 2010 (Y2) were prospectively collected and retrospectively analyzed. Of 1,366 PCIs performed over 2 years, 0.1% in Y1 and 28.7% in Y2 were performed by TR access. No major complications were identified in 194 consecutive patients undergoing TR PCI, and combined bleeding and vascular complication rates were lower in Y2 versus Y1 (0.7% vs 2.0%, p = 0.05). Patients treated in Y2 versus Y1 and by TR versus transfemoral approach required slightly more fluoroscopy but similar contrast volumes and had similar procedural durations, lengths of stay, and predischarge mortality rates. PCI success rates were 97% in Y1, 97% in Y2, and 98% in TR cases. TR PCIs were performed by 13 cardiology fellows and 9 attending physicians, none of whom routinely performed TR PCI previously. In conclusion, de novo establishment of a TR program improved PCI safety at a teaching hospital. TR programs are likely to improve PCI safety at other teaching hospitals and should be established in all cardiology fellowship training programs.

Takotsubo cardiomyopathy in a patient with previously undiagnosed hypertrophic cardiomyopathy with obstruction.

Takotsubo cardiomyopathy (TCM) is usually characterized by left ventricular anteroapical dysfunction in the absence of significant coronary disease commonly precipitated by an emotional or stressful trigger. Hypertrophic cardiomyopathy (HCM) is usually diagnosed on the basis of symptoms, family history, echocardiography, or by the presence of a characteristic murmur. We report a unique case of TCM occurring in a patient with previously undiagnosed HCM with left ventricular outflow tract (LVOT) obstruction who presented with an acute coronary syndrome and ultimately underwent successful alcohol septal ablation. The potential pathophysiologic correlations are discussed.

Comparison of Lipid Deposition at Coronary Bifurcations Versus at Nonbifurcation Portions of Coronary Arteries as Determined by Near-Infrared Spectroscopy

Atherosclerosis has been shown to develop preferentially at sites of coronary bifurcation, yet culprit lesions resulting in ST-elevation myocardial infarction do not occur more frequently at these sites. We hypothesized that these findings can be explained by similarities in intracoronary lipid and that lipid and lipid core plaque would be found with similar frequency in coronary bifurcation and nonbifurcation segments. One hundred seventy bifurcations were identified, 156 of which had comparative nonbifurcation segments proximal and/or distal to the bifurcation. We compared lipid deposition at bifurcation and nonbifurcation segments in coronary arteries using near-infrared spectroscopy (NIRS), a novel method for the in vivo detection of coronary lipid. Any NIRS signal for the presence of lipid was found with similar frequency in bifurcation and nonbifurcation segments (79% vs 74%, p = NS). Lipid core burden index, a measure of total lipid quantity indexed to segment length, was similar across bifurcation segments as well as their proximal and distal controls (lipid core burden index 66.3 ± 106, 67.1 ± 116, and 66.6 ± 104, p = NS). Lipid core plaque, identified as a high-intensity focal NIRS signal, was found in 21% of bifurcation segments, and 20% of distal nonbifurcation segments (p = NS). In conclusion, coronary bifurcations do not appear to have higher levels of intracoronary lipid or lipid core plaque than their comparative nonbifurcation regions.