Tailored risk assessment of 90-day acute heart failure readmission or all-cause death to heart failure with preserved versus reduced ejection fraction.

BACKGROUND: After incident heart failure (HF) admission, patients are vulnerable to readmission or death in the 90-day post-discharge. Although risk models for readmission or death incorporate ejection fraction (EF), patients with HF with preserved EF (HFpEF) and those with HF with reduced EF (HFrEF) represent distinct cohorts. To better assess risk, this study developed machine learning models and identified risk factors for the 90-day acute HF readmission or death by HF subtype. METHODS AND RESULTS: Approximately 1965 patients with HFpEF and 1124 with HFrEF underwent an index admission. Acute HF rehospitalization or death occurred in 23% of HFpEF and 28% of HFrEF groups. Of the 101 variables considered, multistep variable selection identified 24 and 25 significant factors associated with 90-day events in HFpEF and HFrEF, respectively. In addition to risk factors common to both groups, factors unique to HFpEF patients included cognitive dysfunction, low-pulse pressure, ß-blocker, and diuretic use, and right ventricular dysfunction. In contrast, factors unique to HFrEF patients included a history of arrhythmia, acute HF on presentation, and echocardiographic characteristics like left atrial dilatation or elevated mitral E/A ratio. Furthermore, the model tailored to HFpEF (area under the curve [AUC] = 0.770; 95% confidence interval [CI] 0.767-0.774) outperformed a model for the combined groups (AUC = 0.759; 95% CI 0.756-0.763). CONCLUSION: The UF 90-day post-discharge acute HF Re admission or Death Risk Assessment (UF90-RADRA) models help identify HFpEF and HFrEF patients at higher risk who may require proactive outpatient management.

Predicting 90 day acute heart failure readmission and death using machine learning-supported decision analysis.

Readmission or death soon after heart failure (HF) admission is a significant problem. Traditional analyses for predicting such events often fail to consider the gamut of characteristics that may contribute- tending to focus on 30-day outcomes even though the window of increased vulnerability may last up to 90 days. Risk assessments incorporating machine learning (ML) methods may be better suited than traditional statistical analyses alone to sort through multitude of data in the electronic health record (EHR) and identify patients at higher risk. HYPOTHESIS: ML-based decision analysis may better identify patients at increased risk for 90-day acute HF readmission or death after incident HF admission. METHODS AND RESULTS: Among 3189 patients who underwent index HF hospitalization, 15.2% experienced primary or acute HF readmission and 11.5% died within 90 days. For risk assessment models, 98 variables were considered across nine data categories. ML techniques were used to help select variables for a final logistic regression (LR) model. The final model's AUC was 0.760 (95% CI 0.752 to 0.767), with sensitivity of 83%. This proved superior to an LR model alone [AUC 0.744 (95% CI 0.732 to 0.755)]. Eighteen variables were identified as risk factors including dilated inferior vena cava, elevated blood pressure, elevated BUN, reduced albumin, abnormal sodium or bicarbonate, and NT pro-BNP elevation. A risk prediction ML-based model developed from comprehensive characteristics within the EHR can efficiently identify patients at elevated risk of 90-day acute HF readmission or death for whom closer follow-up or further interventions may be considered.

Effect of Elevated Calcium Score on Normal Myocardial Perfusion Study on Clinician Management of Coronary Artery Disease Risk Factors.

Elevated coronary artery calcification (CAC) scores are associated with higher cardiovascular (CV) risk even with normal stress myocardial perfusion imaging (MPI). Whether referring providers appropriately manage subclinical CV disease is unclear. We hypothesized that ordering clinicians would intensify medical therapy for CV disease in response to normal MPI and CAC ≥ 300. We conducted a cohort study on patients without known CV disease who underwent MPI and CAC scoring. Medical management of CV disease and clinical outcomes were assessed. Of 299 patients who underwent stress MPI, 62 patients had normal MPI and CAC ≥ 300. Documentation of elevated CAC score was noted in the final interpretation for 52% (n = 32) of MPI reports. During follow-up, treatment change in aspirin, cholesterol medications, and/or antihypertensive medication was made in 40% of these patients. Aspirin use increased from 71% to 82% (P < 0.001); statin use increased from 68% to 76% (P < 0.001). Several patients remained on suboptimal lipid or antiplatelet regimens without documented contraindication. Among patients with normal MPI, many have CAC ≥ 300. Not all MPI reports adequately call attention to this finding associated with elevated CV risk. Despite the elevated CAC score, some patients were not optimized medically.

Electronic consults for improving specialty care access for veterans.

OBJECTIVES: We adopted e-consults within an active referral management (ARM) process for our Veterans Health Administration (VHA) outpatient cardiology clinic to reduce clinic wait times. STUDY DESIGN: Prospective multiphase cohort study. METHODS: Our ARM process consisted of reviewing all incoming consult requests for our outpatient clinic and triaging the requests to either an e-consult or a clinic visit. The primary outcome was wait time for an appointment in our clinic. RESULTS: Median wait time prior to the ARM process was 24 days. After implementation of the ARM process, wait times decreased to 13 days (46% reduction). Approximately 60% of incoming consults could be triaged into e-consults, predominantly by managing stable diseases or minor symptoms. CONCLUSIONS: E-consults and ARM of clinical referrals were effective at reducing wait times for our outpatient VHA cardiology clinic. The majority of clinical referrals could be handled through an e-consult and did not require an in-person clinic visit.

Mortality implications of lower DBP with lower achieved systolic pressures in coronary artery disease: long-term mortality results from the INternational VErapamil-trandolapril STudy US cohort.

OBJECTIVES: A goal SBP 120 mmHg or less reduced mortality in high-risk Systolic Blood Pressure Intervention Trial patients; however, mortality implications of concomitant DBP lowering in coronary artery disease (CAD) are uncertain. We examined the relationship between DBP lowering and all-cause mortality with lower achieved SBPs in a large cohort. METHODS: We categorized 17 131 hypertensive patients from the INternational VErapamil-trandolapril STudy US cohort, aged at least 50 years with CAD, by mean achieved SBP (<120, 120 to <130, 130 to <140, and ≥140 mmHg) and DBP tertiles (low, middle, and high per SBP category) during active follow-up. Long-term mortality was determined via National Death Index. Multivariable Cox regression was performed to investigate the impact of DBP lowering among all SBP categories and within each SBP category. RESULTS: There were 6031 deaths over mean follow-up of 11.6 years (198 352 patient-years). In unadjusted analyses, achieving DBP in the lowest tertile portended greatest mortality risk across all SBP categories. In multivariate analysis, using SBP 120 to less than 130 mmHg, DBP at least 79 mmHg as reference (mortality nadir), achieving DBP in the lowest tertile (DBP < 69 mmHg) was associated with excess mortality risk among those with SBP less than 120 mmHg (adjusted hazard ratio 1.60; 95% confidence interval, 1.33-1.91). However, among those with SBP 120 to less than 140 mmHg, adjusted mortality risk did not differ significantly with low DBPs. Among those with SBP at least 140 mmHg, mortality risk remained high regardless of DBP. CONCLUSION: In older CAD patients, the mortality risk related to excess DBP lowering is accentuated in those achieving intensive SBP control less than 120 mmHg, raising concerns about intensive SBP lowering in these patients.

Revascularization and outcomes in Veterans with moderate to severe ischemia on myocardial perfusion imaging.

BACKGROUND: The prevalence of ischemia on nuclear myocardial perfusion imaging (MPI) has been decreasing. Recent research has questioned the benefit of invasive revascularization for patients with moderate to severe ischemia. We hypothesized that patients with moderate to severe ischemia could routinely undergo successful revascularization. METHODS: We analyzed data from 544 patients who underwent an MPI at a single academic Veterans Affairs Medical Center. Patients with moderate to severe ischemia, defined as a summed difference score (SDS) 8 or greater, were compared to the rest of the cohort. RESULTS: Of the total cohort (n = 544), 39 patients had MPI studies with resultant moderate to severe ischemia. Patients with ischemia were more likely to develop coronary artery disease (74.4% versus 38.8%, P < 0.0001) and have successful revascularization (38.5% versus 4.0%, P < 0.0001) during the following year. Revascularization was attempted in 31 patients with moderate to severe ischemia, though only 15 (47%) of these attempts were successful. Ischemia was predictive of myocardial infarction (5.1% versus 0.8%, P = 0.01) within 1 year. CONCLUSION: Moderate to severe ischemia is an uncommon finding in a contemporary nuclear laboratory. Among patients with ischemia, revascularization is typically attempted but is frequently unsuccessful. TRIAL REGISTRATION: This trial does not appear on a registry as it is neither randomized nor prospective.

Comparative accuracy of supine-only and combined supine-prone myocardial perfusion imaging in men.

BACKGROUND: Combined supine-prone myocardial perfusion imaging (CSP MPI) has been shown to reduce attenuation artifact in comparison to supine-only (SU) MPI in mixed-gender populations with varying risk for coronary artery disease (CAD), often where patients served as their own controls. However, there is limited direct comparison of these imaging strategies in men. METHODS: 934 male patients underwent CSP or SU MPI. Diagnostic certainty of interpretation was compared. Within the cohort, 116 were referred for left heart catheterization (LHC) to assess for CAD. Sensitivity, specificity, and area under the curve (AUC) were compared with additional analysis based on body mass index (BMI). RESULTS: 597 patients completed the SU protocol and 337 patients completed the CSP protocol. Equivocal studies were seen more frequently in the SU group (13%) than in the CSP group (4%, P < .001). At catheterization, the specificity for CSP MPI of 70% was higher than 40% for SU MPI (P = .032). The CSP AUC (0.80 ± 0.06) was significantly larger than SU AUC (0.57 ± 0.05, P = .004). CSP specificity was significantly higher in obese patients. CONCLUSIONS: CSP MPI increases diagnostic certainty and improves test accuracy for CAD detection in men with CAD risk factors, especially obese patients, compared to SU MPI.

Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: a systematic review and meta-analysis.

BACKGROUND: Potential cardiovascular (CV) risks of testosterone replacement therapy (TRT) are currently a topic of intense interest. However, no studies have addressed CV risk as a function of the route of administration of TRT. METHODS: Two meta-analyses were conducted, one of CV adverse events (AEs) in 35 randomized controlled trials (RCTs) of TRT lasting 12 weeks or more, and one of 32 studies reporting the effect of TRT on serum testosterone and dihydrotestosterone (DHT). RESULTS: CV risks of TRT: Of 2,313 studies identified, 35 were eligible and included 3,703 mostly older men who experienced 218 CV-related AEs. No significant risk for CV AEs was present when all TRT administration routes were grouped (relative risk (RR) = 1.28, 95% confidence interval (CI): 0.76 to 2.13, P = 0.34). When analyzed separately, oral TRT produced significant CV risk (RR = 2.20, 95% CI: 1.45 to 3.55, P = 0.015), while neither intramuscular (RR = 0.66, 95% CI: 0.28 to 1.56, P = 0.32) nor transdermal (gel or patch) TRT (RR = 1.27, 95% CI: 0.62 to 2.62, P = 0.48) significantly altered CV risk. Serum testosterone/DHT following TRT: Of 419 studies identified, 32 were eligible which included 1,152 men receiving TRT. No significant difference in the elevation of serum testosterone was present between intramuscular or transdermal TRT. However, transdermal TRT elevated serum DHT (5.46-fold, 95% CI: 4.51 to 6.60) to a greater magnitude than intramuscular TRT (2.20-fold, 95% CI: 1.74 to 2.77). CONCLUSIONS: Oral TRT produces significant CV risk. While no significant effects on CV risk were observed with either injected or transdermal TRT, the point estimates suggest that further research is needed to establish whether administration by these routes is protective or detrimental, respectively. Differences in the degree to which serum DHT is elevated may underlie the varying CV risk by TRT administration route, as elevated serum dihydrotestosterone has been shown to be associated with CV risk in observational studies.

Safety of magnetic resonance imaging in patients with permanent pacemakers: a collaborative clinical approach.

OBJECTIVE: This study aimed to characterize the interactions of pacemakers with magnetic resonance imaging (MRI) and to identify device characteristics that could predict adverse interactions. BACKGROUND: The safety of MRI in patients with indwelling pacemaker systems remains uncertain. Previous studies demonstrated safety in most patients, but unpredictable, potentially concerning changes in pacemaker behavior have occurred. METHODS: We prospectively studied patients with pacemaker devices in situ who were not pacemaker dependent and in whom MRI was essential for adequate diagnosis and treatment. All patients were monitored by electrocardiography and pulse oximetry during scanning; devices were interrogated and cardiac enzymes were measured before and after scanning. RESULTS: Of 32 patients studied (46 MRI examinations), 28 patients had a dual-chamber system and one had a biventricular device. Regions scanned were the head and spine. Devices were reprogrammed to asynchronous pacing or sense-only mode in all except six patients before MRI. During six scanning episodes (five patients), "power-on" resetting of the device was noted. Magnet-mode pacing was noted during four episodes (three patients). Occasional premature ventricular contractions were noted in one patient. No significant changes in battery voltage, sensed P wave and R wave, pacing thresholds, lead impedance, or cardiac enzymes were noted immediately after MRI or at 1-month follow-up. CONCLUSIONS: Overall, no significant changes were seen in pacemaker device function, and no adverse clinical events were observed. A minority of patients with older devices had unpredictable changes in device behavior, which stresses the need for close monitoring during and careful device interrogation after scanning.

Success of ablation for atrial fibrillation in isolated left ventricular diastolic dysfunction: a comparison to systolic dysfunction and normal ventricular function.

BACKGROUND: The efficacy of radiofrequency ablation for atrial fibrillation (AF) in patients with left ventricular (LV) systolic dysfunction and isolated diastolic dysfunction is uncertain. METHODS AND RESULTS: A prospective cohort of patients with normal and abnormal LV function underwent ablation for antiarrhythmic drug (AAD)-refractory AF. Three groups were compared: 111 patients with systolic dysfunction, defined as LV ejection fraction (LVEF) ≤40%; 157 patients with isolated diastolic dysfunction but preserved LVEF ≥50%; and 100 patients with normal LV function. The primary end point was AAD-free AF elimination at 1 year after ablation. This end point was achieved in 62% of patients with systolic dysfunction, 75% of those with diastolic dysfunction, and 84% of controls (P=0.007). AF control on or off AADs was achieved in 76% of patients with systolic dysfunction, 85% of those with diastolic dysfunction, and 89% of controls (P=0.08). In the systolic dysfunction group, 49% experienced an increase in LVEF by ≥5% after ablation, of which 64% achieved normal LVEF. In the diastolic dysfunction group, 30% of patients demonstrated at least 1 grade improvement in diastolic dysfunction. Multivariable analysis demonstrated an increased relative risk of arrhythmia recurrence of 1.8 (95% CI, 1.1 to 3.1; P=0.02) in systolic dysfunction and 1.7 (1.0 to 2.7; P=0.04) in isolated diastolic dysfunction compared with normal function. CONCLUSIONS: Although an ablative approach for AF in patients with systolic or diastolic dysfunction is associated with an increased long-term recurrence risk, there is potential for substantial quality-of-life improvement and LV functional benefit.

Differential outcome of cardiac resynchronization therapy in ischemic cardiomyopathy and idiopathic dilated cardiomyopathy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a therapy of proven benefit in patients with advanced heart failure. Identifying potential responders remains challenging, and whether the etiology of the heart failure is related to the potential hemodynamic benefit and long-term outcome of CRT is unclear. OBJECTIVE: The purpose of this study was to evaluate whether heart failure etiology (ischemic cardiomyopathy [ICM] vs nonischemic dilated cardiomyopathy [DCM]) was associated with CRT outcome and implantable cardioverter-defibrillator (ICD) shocks. METHODS: The study included 503 CRT recipients (CRT-D 90%) in a longitudinal CRT database: ICM (n = 312) and DCM (n = 191). Clinical variables and echocardiographic measures preimplant and postimplant were collected. Actuarial survival and ICD therapy data were assessed with Kaplan-Meier curve and log rank tests. RESULTS: Pre-CRT, ICM patients were older and had higher creatinine levels (P <.001). At median follow-up of 7.1 months, the DCM group experienced greater improvement in left ventricular ejection fraction (8.3% ± 10% vs 6.2% ± 10%, P = .05) and left ventricular end-diastolic volumes than did those with ICM (-28%.4 ± 53 mL vs -15.3 ± 46 mL, P = .024). Survival estimates at 4 years were 55% for ICM and 77% for DCM groups (P <.001), respectively, whereas no significant difference in the incidence of appropriate/inappropriate ICD shocks was observed. The ICM group remained at higher risk for death compared to the DCM group after controlling for preimplant variables (hazard ratio 1.6, 95% confidence interval 1.1-2.3, P = .008). CONCLUSION: In response to CRT and in contrast to ICM, DCM patients experienced greater improvement in left ventricular systolic function and reverse remodeling while also sustaining a greater survival benefit.

Long-term outcome of atrial fibrillation ablation: impact and predictors of very late recurrence.

INTRODUCTION: Ablation eliminates atrial fibrillation (AF) in studies with 1 year follow-up, but very late recurrences may compromise long-term efficacy. In a large cohort, we sought to describe the determinants of delayed recurrence after AF ablation. METHODS AND RESULTS: Seven hundred and seventy-four patients with AF (428 paroxysmal [PAF, 55%] and 346 persistent or longstanding persistent [PersAF, 45%]) underwent wide area circumferential ablation (WACA, 62%) or pulmonary vein isolation (38%). Over 3.0 ± 1.9 years, there were 135 recurrences in PAF patients and 142 in PersAF patients. AF elimination was achieved in 61% of patients with PersAF at 2 years after last ablation and in 71% of patients with PAF (P = 0.04). This finding was related to a higher initial rate of very late recurrence in PersAF. From 1.0 to 2.5 years, the recurrence increased by 20% (from 37% to 57%) in PersAF patients versus only 12% (from 27% to 39%) in PAF patients. Independent predictors of overall recurrence included diabetes (HR 1.9 [1.3-2.9], P = 0.002) and PersAF (HR 1.6 [1.2-2.0], P < 0.001). Independent predictors of very late recurrence included PersAF (HR 1.7 [1.1-2.7], P = 0.018) and WACA (HR 1.8 [1.1-2.7], P = 0.018), while diabetes came close to significance. In PAF patients, left atrial size >45 mm was identified as an AF-type specific predictor (HR 2.4 [1.3-4.7], P = 0.009), whereas in PersAF patients, no unique predictors were identified. CONCLUSION: Late recurrences reduced the long-term efficacy of AF ablation, particularly in patients with PersAF and underlying cardiovascular diseases.

Long-term quality of life after ablation of atrial fibrillation the impact of recurrence, symptom relief, and placebo effect.

OBJECTIVES: We sought to determine the relationship between atrial fibrillation (AF) ablation efficacy, quality of life (QoL), and AF-specific symptoms at 2 years. BACKGROUND: Although the primary goal of AF ablation is QoL improvement, this effect has yet to be demonstrated in the long term. METHODS: A total of 502 symptomatic AF ablation recipients were prospectively followed for recurrence, QoL, and AF symptoms. RESULTS: In 323 patients with 2 years of follow-up, 72% achieved AF elimination off antiarrhythmic drugs (AADs), 15% achieved AF control with AADs, and 13% had recurrent AF. The physical component summary scores of the Medical Outcomes Study Short Form 36 increased from 58.8 +/- 20.1 to 76.2 +/- 19.2 (p < 0.001) and the mental component summary scores of the Short Form 36 increased from 65.3 +/- 18.6 to 79.8 +/- 15.8 (p < 0.001). Post-ablation QoL improvements were noted across ablation outcomes, including recurrent AF (change in physical component summary: 12.1 +/- 19.7 and change in mental component summary: 9.7 +/- 17.9), with no significant differences in QoL improvement across 3 ablative efficacy outcomes. However, in 103 patients who completed additional assessment with Mayo AF Symptom Inventories (on a scale of 0 to 48), those with AF elimination off AADs had a change in AF symptom frequency score of -9.5 +/- 6.3, which was significantly higher than those with AF controlled with AADs (-5.6 +/- 3.8, p = 0.03) or those with recurrent AF (-3.4 +/- 8.4, p = 0.02). Independent predictors of limited QoL improvement included higher baseline QoL, obesity, and warfarin use at follow-up. CONCLUSIONS: AF ablation produces sustained QoL improvement at 2 years in patients with and without recurrence. AF-specific symptom assessment more accurately reflects ablative efficacy.

Upgrade and de novo cardiac resynchronization therapy: impact of paced or intrinsic QRS morphology on outcomes and survival.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves outcomes in patients with left bundle branch block (LBBB), but the benefits of CRT in patients with other QRS morphologies or previous pacing are uncertain. OBJECTIVE: The purpose of this study was to describe outcomes in patients with prior right ventricular pacing and non-LBBB morphologies. METHODS: We studied 505 patients who underwent de novo CRT (n = 338) or CRT upgrade (n = 167). De novo patients were categorized by underlying QRS morphology: LBBB (67%), right bundle branch block (RBBB; 11%), intraventricular conduction delay (IVCD; 13%), and QRS <120 ms (9%). Upgrade patients were categorized by the percentage of previous ventricular pacing. RESULTS: Patients were followed for death over a median of 2.6 years (interquartile range 1.6-4.0). New York Heart Association (NYHA) functional class and echocardiographic improvements were similar in de novo and upgrade patients. However, within the de novo group, NYHA improvements were less in patients with RBBB (0.3 +/- 0.8; P = .014) or IVCD (0.2 +/- 0.7; P = .001) than in those with LBBB (0.7 +/- 0.8). These patients had less left ventricular functional improvement as well. Survival was comparable after de novo versus upgrade CRT (61% vs 63% at 4 years; P = .906). No clinical or survival differences were noted in upgrade patients based on the percentage of previous pacing. However, survival in de novo CRT recipients with RBBB (32%) was lower than in those with LBBB (66%; P <.001), and RBBB independently predicted death (hazard ratio 3.5, confidence interval 1.9-6.5; P <.001). CONCLUSION: RBBB and IVCD result in less clinical improvement or worsened survival after CRT. Additional selection criteria may be beneficial in identifying potential responders with RBBB, IVCD, or narrow QRS.

Dollars and stents: the economics of drug-eluting stents.

By averting restenoses, drug-eluting stents (DES) reduce the need for repeat revascularization procedures and improve quality of life. Large, randomized clinical trials including the Sirolimus-Eluting Balloon Expandable Stent in Treatment of Patients With De Novo Native Coronary Artery Lesions (SIRIUS) suggest that DES may be cost-effective to the Medicare system over time. However, the high cost of DES and the loss of revenues from revascularization procedures coupled with inadequate Medicare reimbursement are likely to have adverse effects on hospitals, making it hard to meet their bottom line. Key contributors to this problem include the unequal distribution of Medicare reimbursement based on diagnosis-related groups or diagnosis-related group calculations and the lack of price competition for DES. The economic burden of restenoses, the efficacy of DES in averting restenoses, the cost-effectiveness of DES, and the interaction of Medicare, DES manufacturers, and hospitals are reviewed. Using specific cost-containment strategies, hospitals can better maneuver the financial barriers to optimize DES utilization.