Long-term outcomes of heart transplantation in adults with congenital heart disease: The impact of single-ventricle versus biventricular physiology.

Objective: Congenital heart disease is a risk factor for mortality after orthotopic heart transplantation; however, the impact of preoperative circulation type and primary congenital heart disease diagnosis remains poorly delineated. Methods: We retrospectively reviewed patients with adult congenital heart disease aged 16 years or more who underwent orthotopic heart transplantation at our institution between 2008 and 2022. Patients were categorized as having single-ventricle or biventricular circulation. The primary end point was 5-year post-transplant survival. Results: Sixty-one patients with adult congenital heart disease (single-ventricle: n = 26 [42.6%], biventricular: n = 35 [57.4%]) underwent orthotopic heart transplantation at 33.7 [interquartile range, 19.1-48.7] years. The most common congenital heart disease diagnosis was hypoplastic left heart syndrome (n = 11, 42.3%) in the single-ventricle group and congenitally corrected transposition of the great arteries (n = 7, 20.0%) in the biventricular group. Twenty-four patients previously underwent Fontan palliation. At transplant, patients in the single-ventricle group were younger (18.5 [interquartile range, 17.6-32.3] years vs 45.0 [interquartile range, 33.0-52.2] years, P < .001) and more likely to have biopsy-proven cirrhosis (46.2% vs 14.3%, P = .01) and protein-losing enteropathy (42.3% vs 2.9%, P < .001). Patients in the single-ventricle group also had longer bypass times (223.4 ± 65.3 minutes vs 187.4 ± 59.5 minutes, P = .03) and longer durations of mechanical ventilatory support (3.5 [interquartile range, 2.0-6.0] days vs 1.0 [interquartile range, 1.0-2.0] days, P < .001). Operative mortality was comparable (11.5% vs 8.6%, P = 1). Median follow-up was 6.0 [interquartile range, 2.4-10.0] years. Five-year survival was worse in the single-ventricle group (66.0% ± 10.0% vs 91.3% ± 4.8%, P = .03), as was freedom from major rejection (58.3% ± 10.2% vs 84.0% ± 6.6%, P = .02). In univariable analysis, hypoplastic left heart syndrome and Fontan circulation were risk factors for post-transplant mortality (hypoplastic left heart syndrome: hazard ratio, 5.0, P < .001; Fontan: hazard ratio, 3.5, P = .03). Conclusions: Adult patients with congenital heart disease undergoing heart transplant with single-ventricle physiology experienced a more complicated post-transplant course, with worse long-term survival and freedom from rejection. Multicenter studies are required to guide orthotopic heart transplantation decision-making in this complex cohort.

Myocardial Recovery With HeartMate 3 Left Ventricular Assist Device: An Attainable Goal That Needs Better Precision.

Despite advances in our understanding of myocardial recovery among left ventricular assist device (LVAD) patients, with 10-30% of patients achieving substantial myocardial improvement, the rates of LVAD support cessation remain extremely low (1-2%). These numbers are in stark contrast to clinical trial data where successful LVAD cessation is reported in up to 47% of patients. The majority of LVAD programs lack structured recovery programs and targeted protocols, likely underscoring the heterogeneity that exists among LVAD patients with myocardial recovery. This perspective summarizes the current medical and surgical challenges with respect to 1) identifying the appropriate candidates for LVAD cessation; 2) methods to wean LVAD support; 3) reviewing surgical techniques for cessation of current generation HeartMate 3 LVAD; and 4) approaching shared decision making for LVAD cessation between patients and providers given the uncertainties that remain in the field.

A RE-AIM Evaluation of a Visualization-Based Electronic Patient-Reported Outcome System.

OBJECTIVES: Health care systems are primarily collecting patient-reported outcomes (PROs) for research and clinical care using proprietary, institution- and disease-specific tools for remote assessment. The purpose of this study was to conduct a Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) evaluation of a scalable electronic PRO (ePRO) reporting and visualization system in a single-arm study. METHODS: The "mi.symptoms" ePRO system was designed using gerontechnological design principles to ensure high usability among older adults. The system enables longitudinal reporting of disease-agnostic ePROs and includes patient-facing PRO visualizations. We conducted an evaluation of the implementation of the system guided by the RE-AIM framework. Quantitative data were analyzed using basic descriptive statistics, and qualitative data were analyzed using directed content analysis. RESULTS: Reach-the total reach of the study was 70 participants (median age: 69, 31% female, 17% Black or African American, 27% reported not having enough financial resources). Effectiveness-half (51%) of participants completed the 2-week follow-up survey and 36% completed all follow-up surveys. Adoption-the desire for increased self-knowledge, the value of tracking symptoms, and altruism motivated participants to adopt the tool. Implementation-the predisposing factor was access to, and comfort with, computers. Three enabling factors were incorporation into routines, multimodal nudges, and ease of use. Maintenance-reinforcing factors were perceived usefulness of viewing symptom reports with the tool and understanding the value of sustained symptom tracking in general. CONCLUSION: Challenges in ePRO reporting, particularly sustained patient engagement, remain. Nonetheless, freely available, scalable, disease-agnostic systems may pave the road toward inclusion of a more diverse range of health systems and patients in ePRO collection and use.

Detecting early physiologic changes through cardiac implantable electronic device data among patients with COVID-19.

Background: Cardiac implantable electronic devices (CIEDs) may enable early identification of COVID-19 to facilitate timelier intervention. Objective: To characterize early physiologic changes associated with the onset of acute COVID-19 infection, as well as during and after acute infection, among patients with CIEDs. Methods: CIED sensor data from March 2020 to February 2021 from 286 patients with a CIED were linked to clinical data from electronic health records. Three cohorts were created: known COVID-positive (n = 20), known COVID-negative (n = 166), and a COVID-untested control group (n = 100) included to account for testing bias. Associations between changes in CIED sensors from baseline (including HeartLogic index, a composite index predicting worsening heart failure) and COVID-19 status were evaluated using logistic regression models, Wilcoxon signed rank tests, and Mann-Whitney U tests. Results: Significant differences existed between the cohorts by race, ethnicity, CIED device type, and medical admissions. Several sensors changed earlier for COVID-positive vs COVID-negative patients: HeartLogic index (mean 16.4 vs 9.2 days [P = .08]), respiratory rate (mean 8.5 vs 3.9 days [P = .01], and activity (mean 8.2 vs 3.5 days [P = .008]). Respiratory rate during the 7 days before testing significantly predicted a positive vs negative COVID-19 test, adjusting for age, sex, race, and device type (odds ratio 2.31 [95% confidence interval 1.33-5.13]). Conclusion: Physiologic data from CIEDs could signal early signs of infection that precede clinical symptoms, which may be used to support early detection of infection to prevent decompensation in this at-risk population.

Remote Cardiac Monitoring in Patients With Heart Failure: A Review.

Importance: Heart failure (HF) is often characterized by an insidious disease course leading to frequent rehospitalizations and a high use of ambulatory care. Remote cardiac monitoring is a promising approach to detect worsening HF early and intervene prior to an overt decompensation. Observations: Recently, a multitude of novel technologies for remote cardiac monitoring (RCM) in patients with HF have been developed and are undergoing clinical trials. This development has been accelerated by the COVID-19 pandemic. Conclusions and Relevance: This review summarizes the major clinical trials on RCM in patients with HF and present the most recent developments in noninvasive and invasive RCM technologies.

Impact of the new UNOS donor heart allocation system on waitlist outcomes and early posttransplant mortality among adults with congenital heart disease.

Adults with congenital heart disease (ACHD) experience worse waitlist outcomes and higher early posttransplant mortality compared to non-ACHD patients. On October 18, 2018; the UNOS donor heart allocation system was redesigned giving unique listing status to ACHD patients. The impact of this change on outcomes in transplant-listed patients is unstudied. Using the Scientific Registry of Transplant Recipients (SRTR) we compared ACHD patients listed for the first-time for heart transplantation from two eras of equal duration. We analyzed waitlist outcomes, posttransplant mortality and length of stay among ACHD patients in both eras and between ACHD and non-ACHD patients in the new era. Of 12 723 listed patients, 535 had ACHD (293 in the new era) and 12 188 did not (6258 in the new era). A total of 163 (56%) ACHD patients in the new era versus 150 (62%) in the prior era were transplanted; 11 (3.8%) versus 15 (6.2%) died on the waitlist; 32 (11%) versus 35 (14%) were delisted and 15 (9.2%) versus 19 (12.7%) died within 30 days of transplant, respectively. The new UNOS donor heart allocation system improved waitlist time and decreased the proportion not transplanted during the first 300 days after listing among ACHD patients without altering early posttransplant outcomes or significantly changing the gap in outcomes compared to non-ACHD patients.

Deep significance clustering: a novel approach for identifying risk-stratified and predictive patient subgroups.

OBJECTIVE: Deep significance clustering (DICE) is a self-supervised learning framework. DICE identifies clinically similar and risk-stratified subgroups that neither unsupervised clustering algorithms nor supervised risk prediction algorithms alone are guaranteed to generate. MATERIALS AND METHODS: Enabled by an optimization process that enforces statistical significance between the outcome and subgroup membership, DICE jointly trains 3 components, representation learning, clustering, and outcome prediction while providing interpretability to the deep representations. DICE also allows unseen patients to be predicted into trained subgroups for population-level risk stratification. We evaluated DICE using electronic health record datasets derived from 2 urban hospitals. Outcomes and patient cohorts used include discharge disposition to home among heart failure (HF) patients and acute kidney injury among COVID-19 (Cov-AKI) patients, respectively. RESULTS: Compared to baseline approaches including principal component analysis, DICE demonstrated superior performance in the cluster purity metrics: Silhouette score (0.48 for HF, 0.51 for Cov-AKI), Calinski-Harabasz index (212 for HF, 254 for Cov-AKI), and Davies-Bouldin index (0.86 for HF, 0.66 for Cov-AKI), and prediction metric: area under the Receiver operating characteristic (ROC) curve (0.83 for HF, 0.78 for Cov-AKI). Clinical evaluation of DICE-generated subgroups revealed more meaningful distributions of member characteristics across subgroups, and higher risk ratios between subgroups. Furthermore, DICE-generated subgroup membership alone was moderately predictive of outcomes. DISCUSSION: DICE addresses a gap in current machine learning approaches where predicted risk may not lead directly to actionable clinical steps. CONCLUSION: DICE demonstrated the potential to apply in heterogeneous populations, where having the same quantitative risk does not equate with having a similar clinical profile.

Remote Hemodynamic Monitoring Equally Reduces Heart Failure Hospitalizations in Women and Men in Clinical Practice: A Sex-Specific Analysis of the CardioMEMS Post-Approval Study.

BACKGROUND: Response to pharmacological and device-based therapy for heart failure (HF) may vary by sex. We examined sex differences in response to ambulatory hemodynamic monitoring in clinical practice using the CardioMEMS PAS (Post-Approval Study). METHODS: The CardioMEMS PAS was a prospective, single-arm, multicenter, open-label study of 1200 adults with New York Heart Association class III HF and at least 1 HF hospitalization (HFH) within 12 months who underwent pulmonary artery pressure sensor implantation between 2014 and 2017. Changes in pulmonary artery pressure over time were stratified by ejection fraction <40% and sex. Clinical outcomes including HFH rate at 12 months, 1-year mortality, and quality of life were examined in women and men. RESULTS: Four hundred fifty-two women (38% of total) enrolled in the PAS were less likely to be White (78% versus 86%) and more likely to have nonischemic cardiomyopathy (44% versus 34%) and had significantly higher SBP (132 versus 124 mm Hg), mean ejection fraction (44% versus 36%), and pulmonary vascular resistance (3.2 versus 2.6 WU) than men (P<0.001 for all). There were similar reductions in pulmonary artery pressure from baseline to 12 months in both men and women for the whole cohort and for subgroups with HF with reduced ejection fraction and HF with preserved ejection fraction. Both sexes experienced significant decreases in HFH over 12 months (men: HR, 0.46 [95% CI, 0.40-0.52]; women: HR, 0.39 [95% CI, 0.33-0.46]). In adjusted models, there were no significant differences in change in HFH between men and women (interaction P=0.13) or all-cause mortality at 1 year (adjusted HR, 1.25 [95% CI, 0.88-1.77]). CONCLUSIONS: Women and men enrolled in the CardioMEMS PAS had similar reductions from baseline in pulmonary artery pressure over 1 year and experienced similar reductions in HFH. Hemodynamic monitoring provides similar benefit with regard to HF events in both women and men. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02279888.

Advanced heart failure patients supported with ambulatory inotropic therapy: What defines success of therapy?

OBJECTIVE: The objective of this study was to describe the profiles and outcomes of a cohort of advanced heart failure patients on ambulatory inotropic therapy (AIT). BACKGROUND: With the growing burden of patients with end-stage heart failure, AIT is an increasingly common short or long-term option, for use as bridge to heart transplant (BTT), bridge to ventricular assist device (BTVAD), bridge to decision regarding advanced therapies (BTD) or as palliative care. AIT may be preferred by some patients and physicians to facilitate hospital discharge. However, counseling patients on risks and benefits is critically important in the modern era of defibrillators, durable mechanical support and palliative care. METHODS: We retrospectively studied a cohort of 241 patients on AIT. End points included transplant, VAD implantation, weaning of inotropes, or death. The primary outcomes were survival on AIT and ability to reach intended goal if planned as BTT or BTVAD. We also evaluated recurrent heart failure hospitalizations, incidence of ventricular arrhythmias (VT/VF) and indwelling line infections. Unintended consequences of AIT, such reaching unintended end point (e.g. VAD implantation in BTT patient) or worse than expected outcome after LVAD or HT, were recorded. RESULTS: Mean age of the cohort was 60.7 ± 13.2 years, 71% male, with Class III-IV heart failure (56% non-ischemic). Average ejection fraction was 19.4 ± 10.2%, pre-AIT cardiac index was 1.5 ± 0.4 L/min/m2 and 24% had prior ventricular arrhythmias. Overall on-AIT 1-year survival was 83%. Hospitalizations occurred in 51.9% (125) of patients a total of 174 times for worsening heart failure, line complication or ventricular arrhythmia. In the BTT cohort, only 42% were transplanted by the end of follow-up, with a 14.8% risk of death or delisting for clinical deterioration. For the patients who were transplanted, 1-year post HT survival was 96.7%. In the BTVAD cohort, 1-year survival after LVAD was 90%, but with 61.7% of patients undergoing LVAD as INTERMACS 1-2. In the palliative care cohort, only 24.5% of patients had a formal palliative care consult prior to AIT. CONCLUSIONS: AIT is a strategy to discharge advanced heart failure patients from the hospital. It may be useful as bridge to transplant or ventricular assist device, but may be limited by complications such as hospitalizations, infections, and ventricular arrhythmias. Of particular note, it appears more challenging to bridge to transplant on AIT in the new allocation system. It is important to clarify the goals of AIT therapy upfront and continue to counsel patients on risks and benefits of the therapy itself and potential unintended consequences. Formalized, multi-disciplinary care planning is essential to clearly define individualized patient, as well as programmatic goals of AIT.

Cardiac transplantation in adult congenital heart disease with prior sternotomy.

BACKGROUND: Adult congenital heart disease (ACHD) patients who require orthotopic heart transplantation are surgically complex due to anatomical abnormalities and multiple prior surgeries. In this study, we investigated these patients' outcomes using our institutional database. METHODS: ACHD patients who had prior intracardiac repair and subsequent heart transplant were included (2008-2018). Adult patients without ACHD were extracted as a control. A comparison of patients with functional single ventricular (SV) and biventricular (BV) hearts was performed. RESULTS: There were 9 SV and 24 BV patients. The SV group had higher central venous pressure/pulmonary capillary wedge pressure (P = .028), hemoglobin concentration (P = .010), alkaline phosphatase (P = .022), and were more likely to have liver congestion (P = .006). Major complications included infection in 16 (48.5%), temporary dialysis in 12 (36.4%), and graft dysfunction requiring perioperative mechanical support in 7 (21.2%). Overall in-hospital mortality was 15.2%. Kaplan-Meier analysis showed a higher, but not statistically significant, survival after 10 years between the ACHD and control groups (ACHD 84.9% vs. control 67.5%, P = .429). There was no significant difference in 10-year survival between SV and BV groups (78% vs. 88%, P = .467). CONCLUSIONS: Complex ACHD cardiac transplant recipients have a high incidence of early morbidities after transplantation. However, long-term outcomes were acceptable.

Outcomes of Heart Transplantation in Adult Congenital Heart Disease With Prior Intracardiac Repair.

BACKGROUND: The number of patients with adult congenital heart disease (ACHD) who require orthotopic heart transplantation has increased rapidly in the past 2 decades. This study examined heart transplant outcomes of patients with ACHD who had previous cardiac surgery by using data from the United Network for Organ Sharing database. METHODS: Between January 2008 and March 2019, patients with ACHD who underwent previous cardiac surgery and subsequent heart transplantation were identified from the United Network for Organ Sharing database. As a control group, adult patients without congenital heart disease who had previous sternotomy and subsequent heart transplantation were extracted from the database. Propensity score matching was then used to compare outcomes between the 2 groups. RESULTS: There were 793 patients in the ACHD group and 8400 patients in the control group. Among well-matched groups of 486 patients each, 30-day mortality (8.2% vs 3.9%; P = .004) and perioperative need for dialysis (22.7% vs 13.3%; P < .001) were significantly higher in the ACHD group compared with the control group. However, there was no difference in 10-year survival between the groups (ACHD 66.0% vs control 64.1%; log-rank P = .353). CONCLUSIONS: Compared with well-matched patients without ACHD but with previous sternotomy, patients with ACHD and previous intracardiac repair had a higher operative risk but similar 10-year survival.

Using electronic health records for population health sciences: a case study to evaluate the associations between changes in left ventricular ejection fraction and the built environment.

OBJECTIVE: Electronic health record (EHR) data linked with address-based metrics using geographic information systems (GIS) are emerging data sources in population health studies. This study examined this approach through a case study on the associations between changes in ejection fraction (EF) and the built environment among heart failure (HF) patients. MATERIALS AND METHODS: We identified 1287 HF patients with at least 2 left ventricular EF measurements that are minimally 1 year apart. EHR data were obtained at an academic medical center in New York for patients who visited between 2012 and 2017. Longitudinal clinical information was linked with address-based built environment metrics related to transportation, air quality, land use, and accessibility by GIS. The primary outcome is the increase in the severity of EF categories. Statistical analyses were performed using mixed-effects models, including a subgroup analysis of patients who initially had normal EF measurements. RESULTS: Previously reported effects from the built environment among HF patients were identified. Increased daily nitrogen dioxide concentration was associated with the outcome while controlling for known HF risk factors including sex, comorbidities, and medication usage. In the subgroup analysis, the outcome was significantly associated with decreased distance to subway stops and increased distance to parks. CONCLUSIONS: Population health studies using EHR data may drive efficient hypothesis generation and enable novel information technology-based interventions. The availability of more precise outcome measurements and home locations, and frequent collection of individual-level social determinants of health may further drive the use of EHR data in population health studies.

Transition of a Large Tertiary Heart Failure Program in Response to the COVID-19 Pandemic: Changes That Will Endure.

The coronavirus disease 2019 (COVID-19) pandemic imposed severe restrictions on traditional methods of patient care. During the pandemic, the heart failure program at New York-Presbyterian Hospital in New York, NY rapidly and comprehensively transitioned its care delivery model and administrative organization to conform to a new healthcare environment while still providing high-quality care to a large cohort of patients with heart failure, heart transplantation, and left ventricular assist device. In addition to the widespread adoption of telehealth, our program restructured outpatient care, initiating a shared clinic model and introducing a comprehensive remote monitoring program to manage patients with heart failure and heart transplant. All conferences, including administrative meetings, support groups, and educational seminars were converted to teleconferencing platforms. Following the peak of COVID-19, many of the new changes have been maintained, and the program structure will be permanently altered as a lasting effect of this pandemic. In this article, we review the details of our program's transition in the face of COVID-19 and highlight the programmatic changes that will endure.

United network for organ sharing outcomes after heart transplantation for al compared to ATTR cardiac amyloidosis.

Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients.

A Rare Presentation of Cardiomyopathy in Pregnancy.

Our patient presented in her third trimester of pregnancy with new onset of heart failure. A thorough workup in the initial postpartum period with detailed past medical history, advanced imaging modalities, and a multidisciplinary approach revealed a rare and treatable etiology of cardiomyopathy. (Level of Difficulty: Intermediate.).

Impact of durable ventricular assist devices on post-transplant outcomes in adults with congenital heart disease.

BACKGROUND: There are no published data on post-transplant outcomes in durable ventricular assist device (VAD)-supported adult congenital heart disease (ACHD) patients. METHODS: We compared post-transplant outcomes in VAD-supported vs non-VAD-supported ACHD patients using the Scientific Registry of Transplant Recipients. RESULTS: At 1 year, there was no difference in post-transplant mortality between VAD-supported (12 patients) and non-VAD-supported (671 patients) ACHD patients. CONCLUSIONS: In appropriate ACHD patients, VAD use as a bridge to transplant is a reasonable strategy.

Advanced Therapies for Advanced Heart Failure in Women.

Women with advanced heart failure (HF) are underrepresented in trials of short-term and durable mechanical circulatory support although they derive similar benefit. In acute HF, intensive medical and interventional therapies are effective but underutilized. The smaller, newer generation, left ventricular assist devices (LVADs) have increased the feasibility of durable support in women. Women frequently present late, with more comorbidities, emphasizing the need for timely referral. Compared with men, the stroke risk is higher in women with an LVAD. Increased representation in clinical trials and a better understanding of the psychosocial issues affecting women is essential.

Statins and diabetes: the good, the bad, and the unknown.

The ability for statins to reduce major cardiovascular events and mortality has lead to this drug class being the most commonly prescribed in the world. In particular, the benefit of these drugs in type 2 diabetes (T2D) is well established. In February 2012, the Food and Drug Administration released changes to statin safety label to include that statins have been associated with increases in hemoglobin A1C and fasting serum glucose levels. This has stirred much debate in the medical community. Estimate for new onset diabetes from statin treatment is approximately one in 255 patients over four years. The number needed to treat for statin benefit is estimated at one in 40 depending on the population. The mechanism of this link remains unknown. Statins may accelerate progression to diabetes via molecular mechanisms that impact insulin resistance and cellular metabolism of carbohydrates. It remains clear that the benefit of statin therapy outweighs the risk of developing diabetes.

Heart rate in coronary artery disease: should we lower it?

OPINION STATEMENT: Elevated resting heart rate is an independent risk factor for cardiovascular morbidity and mortality in patients with and without coronary artery disease. In patients with known coronary artery disease, elevated heart rate reduces diastolic filling time and increases cardiac workload, resulting in supply demand mismatch with consequent ischemia and angina. While lower heart rate is associated with better prognosis, it is not known if pharmacological reduction in heart rate is beneficial and if heart rate is merely a marker for increased risk and worse outcomes. Certainly, physiologically lower resting heart rate as attained by exercise improves morbidity and mortality. While physiological reduction in heart rate is mainly a manifestation of increased parasympathetic drive, pharmacological reduction of heart rate with beta-blockers is mediated via the sympathetic pathway and associated with mixed outcomes. In addition, beta-blockers have other cardiovascular effects (lowering blood pressure), are metabolically active, and it is unknown if the beneficial effects (if any) are mediated via reduction in heart rate versus other cardiovascular effects. Ivabradine is a new medication that lowers heart rate selectively by inhibiting the I(f) current without other cardiovascular effects, offering for the first time a therapeutic agent that selectively targets heart rate. The medication has shown promise in early trials in patients with heart failure, but it is unclear if this agent will be beneficial in patients with stable coronary artery disease without heart failure.