Mortality and guideline-directed medical therapy in real-world heart failure patients with reduced ejection fraction.

OBJECTIVE: To estimate the prevalence of guideline-directed medical therapy (GDMT) in commercially insured US patients with heart failure with reduced ejection fraction (HFrEF) and examine the effect of GDMT on all-cause mortality. GDMT for HFrEF includes pharmacologic therapies such as ß-blockers (BB), angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin (ARNI), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter inhibitors to reduce morbidity and mortality. METHODS: Patients in the Optum Integrated File from 2007 to 2019Q3, ≥18 years, with history of HFrEF, were identified. Patients prescribed both a BB and either an ACE-I, ARB, or ARNI during 6-month post-diagnosis were assigned to the GDMT cohort. All others were assigned to the not on GDMT cohort. The GDMT cohort was further classified by those patients with a record of prescription fills for both classes of medications concurrently (GDMT concurrent medication fills). Mortality at 2 years was assessed with a Cox regression model accounting for baseline demographics, comorbidities, and diuretic use. RESULTS: This study identified 14 880 HFrEF patients, of which 70% had a record of GDMT, and 57% had a record of concurrent prescriptions. Patients in the not on GDMT cohort had 29% increased risk of mortality versus GDMT (hazard ratio 1.29; 95% CI (1.19-1.40); p < .0001). As a sensitivity analysis, the effect of patients not on GDMT compared to GDMT with concurrent medication fills was more pronounced, with a 37% increased mortality risk. CONCLUSION: In a real-world population of HFrEF patients, inadequate GDMT confers a 29% excess mortality risk over the 2-year follow-up.

Healthcare utilization and guideline-directed medical therapy in heart failure patients with reduced ejection fraction.

Aim: This study examines the effect of guideline-directed medical therapy (GDMT) on healthcare utilization in patients with heart failure with reduced ejection fraction from Optum® Integrated File from 1 January 2007 to 30 June 2020. Materials & methods: Patients with both a beta blocker and either an ACE inhibitor (ACE-I), angiotensin receptor blocker (ARB) or angiotensin receptor neprilysin inhibitor were assigned to the GDMT cohort. All others were not on GDMT. Results: Estimated annual all cause hospitalizations and emergency department visits per 100 patients was 29% (80 vs 62 patients) and 26% higher (54 vs 43 patients; p < 0.0001) and annualized hospital days were longer (1.88 vs 1.64; p = 0.0020) for patients not on GDMT. Conclusion: In a real-world population, heart failure with reduced ejection fraction, patients not optimally managed on GDMT had higher annualized healthcare utilization when compared with patients on GDMT.

Comparison of Survival in Patients With Clinically Significant Tricuspid Regurgitation With and Without Heart Failure (From the Optum Integrated File).

This study aimed to quantify survival rates for patients with tricuspid regurgitation (TR) using real-world data. Several clinical conditions are associated with TR, including heart failure (HF), other valve disease (OVD), right-sided heart disease (RSHD), and others that impact mortality. Optum data from January 1, 2007, through December 31, 2018 included patients age ≥18 years with TR and 12 months of continuous health plan enrollment before TR. Exclusion criteria were end-stage renal disease or known/primary organ pathology. Cohorts were created hierarchically: (1) TR with HF; (2) TR with OVD (no HF); (3) TR with RSHD only (no OVD or HF); (4) TR only. Survival was estimated using a Cox hazard model with an interaction term for TR severity and adjusted for patient demographics and Elixhauser co-morbidities. A total of 33,686 met study inclusion (1) TR with HF (26.6%); (2) TR with OVD (36.7%); (3) TR with RSHD only (17.1%); (4) TR only (19.6%). TR patients (regardless of severity) with HF, OVD or RSHD had an increased risk of mortality compared with patients with TR alone. TR severity was also significantly associated (hazard ratio = 1.33; p = 0.0002) with an increased risk of all-cause mortality. In conclusion, TR severity is significantly associated with an increased risk of all-cause mortality, independent of associated conditions including HF, OVD, or RSHD. In patients with severe TR, the mortality risk is most pronounced for patients who had RSHD without HF or OVD before their TR diagnosis.

Healthcare utilization in clinically significant tricuspid regurgitation patients with and without heart failure.

Aim: This study evaluated how the presence of right-sided heart disease (RSHD), other valve disease (OVD) and heart failure (HF) impacts healthcare utilization in patients with tricuspid valve disease (tricuspid regurgitation [TR]). Materials & methods: Of the 33,686 patients with TR: 6618 (19.6%) had TR-only; 8952 (26.6%) had TR with HF; 12,367 (36.7%) had TR with OVD but no HF; and 5749 (17.1%) had TR with RSHD only. Results: The presence of RSHD, OVD or HF in patients with TR was independently associated with increased annualized hospitalizations, hospital days and costs relative to patients with TR alone. Conclusion: All three co-morbidities were associated with increased healthcare utilization, with HF showing the greatest impact across all measures.

Impact of mitral regurgitation on cardiovascular hospitalization and death in newly diagnosed heart failure patients.

AIMS: Heart failure (HF) carries a poor prognosis, and the impact of concomitant mitral regurgitation (MR) is not well understood. This analysis aimed to estimate the incremental effect of MR in patients newly diagnosed with HF. METHODS AND RESULTS: Data from the IBM® MarketScan® Research Databases were analysed. Included patients had at least one inpatient or two outpatient HF claims. A 6 month post-period after HF index was used to capture MR diagnosis and severity. HF patients were separated into three cohorts: without MR (no MR), not clinically significant MR (nsMR), and significant MR (sMR). Time-to-event analyses were modelled to estimate the clinical burden of disease. The primary outcome was a composite endpoint of death or cardiovascular (CV)-related admission. Secondary outcomes were death and CV hospitalization alone. All models controlled for baseline demographics and co-morbidities. Patients with sMR were at significantly higher risk of either death or CV admission compared with patients with no MR [hazard ratio (HR) 1.26; 95% confidence interval (CI) 1.15-1.39]. When evaluating death alone, patients with sMR had significantly higher risk of death (HR 1.24; 95% CI 1.08-1.43) compared with patients with no MR. When evaluating CV admission alone, patients with MR were at higher risk of hospital admission vs. patients with no MR, and the magnitude was dependent upon the MR severity: sMR (HR 1.55; 95% CI 1.38-1.74) and nsMR (HR 1.23; 95% CI 1.08-1.40). CONCLUSIONS: Evidence of MR in retrospective claims significantly increases the clinical burden of incident HF patients. Time to death and CV hospitalizations are increased when MR is clinically significant.

The economic impact of clinically significant tricuspid regurgitation in a large, administrative claims database.

Aim: This study aimed to quantify the healthcare burden of clinically significant tricuspid regurgitation (TR) in patients with and without heart failure (HF).Materials and Methods: Data were from the IBM MarketScan Research Databases from October 2011 to September 2016. Eligible patients met the following inclusion criteria: age ≥18 with a TR diagnosis, 12 months pre (baseline), and 6 months post (landmark) medical enrollment. The landmark period was used to categorize TR severity, defined as a record of pulmonary hypertension with ascites, lower extremity edema or hepatic insufficiency, or tricuspid valve surgery. Cohorts were defined based on TR etiology and severity: (1) no HF and no clinically significant TR; (2) HF with no clinically significant TR; (3) no HF with clinically significant TR; and (4) HF with clinically significant TR. Outcomes of interest were all-cause hospitalizations, hospital days, and expenditures. Multivariable models were fit for each of the annualized outcomes and adjusted for patient demographics, comorbidities, and other concomitant valve diseases.Results: There were 92,994 patients eligible for analysis. Patients with no HF and no clinically significant TR had the annualized healthcare burden of 0.20 all-cause hospitalizations (approximately one inpatient hospitalization every 5 years), 1.07 hospital days, and $17,478 in expenditures. The presence of clinically significant TR, alone or with HF, significantly increased healthcare utilization and expenditures. For patients with no HF with clinically significant TR, the annualized economic burden increased to 0.41 all-cause hospitalizations, 3.13 hospital days, and $29,985 in expenditures. For patients with HF and clinically significant TR, the annualized economic burden was even greater with 0.59 all-cause hospitalizations, 4.31 hospital days, and $42,255 in expenditures.Conclusion: The presence of clinically significant TR is associated with an increase in healthcare utilization and expenditures, irrespective of the presence of HF.

Twelve-month healthcare utilization and expenditures in Medicare fee-for-service patients with clinically significant mitral regurgitation.

Aim: This study sought to quantify the healthcare burden of Medicare patients with clinically significant mitral regurgitation (sMR). Materials & methods: Proxy definitions were used for sMR, including MR surgery, atrial fibrillation, pulmonary hypertension or >2 echocardiograms. Results: In this study, 11,173 patients had significant degenerative MR (sDMR); 25,402 had significant functional MR (sFMR); and 12,232 had significant uncharacterized MR (sUMR). Patients with sFMR (18,880) were more likely to be hospitalized and present to the emergency department compared with patients with sDMR (9,795) or sUMR (10,587). Annual healthcare expenditures for sMR patients were: US$29,328 for sFMR; US$17,112 for sUMR; and US$12,870 for sDMR. Conclusion: Novel therapeutic interventions merit further evaluation to reduce the substantial healthcare burden of sMR in the Medicare population.

The Economic Impact of Mitral Regurgitation on Patients With Medically Managed Heart Failure.

The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p = 0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p = 0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant.

The healthcare burden of disease progression in medicare patients with functional mitral regurgitation.

Objective: This retrospective database analysis estimated the incremental effect that disease progression from non-clinically significant functional mitral regurgitation (nsFMR) to clinically significant FMR (sFMR) has on clinical outcomes and costs. Methods: Medicare Fee for Service beneficiaries with nsFMR were examined, defined as those with a heart failure diagnosis prior to MR. Patients were classified as ischemic if there was a history of: CAD, AMI, PCI, or CABG. The primary outcome was time to sFMR, defined as pulmonary hypertension, atrial fibrillation, mitral valve surgery, serial echocardiography, or death, using a Cox hazard regression model. Annualized hospitalizations, inpatient hospital days, and healthcare expenditures were also modeled. Results: Patients with IHD had higher risk (Hazard Ratio = 1.22 [1.14-1.30]) for disease progression compared to patients without. The progression cohort had significantly more annual inpatient hospitalizations (non-IHD = 1.32; IHD = 1.40) than the non-progression cohort (non-IHD = 0.36; IHD = 0.34), and significantly more annual inpatient hospital days (non-IHD = 13.07; IHD = 13.52) than the non-progression cohort (non-IHD = 2.29; with IHD = 2.08). The progression cohort had over 3.5-times higher costs vs the non-progression cohort, independent of IHD (non-IHD = $12,798 vs $46,784; IHD = $12,582 vs $49,348). Conclusion: Treating FMR patients earlier in their clinical trajectory may prevent disease progression and reduce high rates of healthcare utilization and expenditures.

Recurrent Cardiogenic Shock Associated with Cannabis Use: Report of a Case and Review of the Literature.

BACKGROUND: The United States has recently undergone increases in the legalization and use of marijuana. There have been previous reports on the association of cannabis use and myocardial dysfunction, however, few on the association with acute stress cardiomyopathy and cardiogenic shock. CASE REPORT: This is a case of a 58-year-old female with a history of inhaled cannabis use, no history of diabetes, and no known history of cardiac disease, that illustrates an association between cannabis use and the recurrent development of stress cardiomyopathy and cardiogenic shock. A review of medical records was performed from two hospitalizations and subsequent outpatient follow-up for similar presentations 6 years apart and review of literature regarding cannabis use and its association with cardiac dysfunction. In separate hospitalizations, the patient presented with clinical findings of cardiogenic shock, severe left ventricular dysfunction with morphologic features of stress cardiomyopathy, and normal coronary angiography. Laboratory results included elevated cardiac biomarkers and urine tetrahydrocannabinol levels > 300 ng/mL. The patient required intensive cardiovascular support, but recovered with normal cardiac function after each event. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As use of cannabis becomes more prevalent, it will be important for physicians to recognize the potential association of cannabis use and acute myocardial dysfunction, and how early treatment may contribute to salutary outcomes.

Percutaneous Repair of Postoperative Mitral Regurgitation After Left Ventricular Assist Device Implant.

Mitral regurgitation commonly improves after implantation of a left ventricular assist device without concomitant valvular repair owing to the mechanical unloading of the left ventricle. However, the development (or persistence) of significant mitral regurgitation after implantation of a left ventricular assist device is associated with adverse clinical events. We present a case of a left ventricular assist device patient who successfully underwent a percutaneous MitraClip procedure for repair of persistent late postoperative mitral insufficiency with demonstrable clinical and hemodynamic improvement.

A Case Series of Biventricular Circulatory Support Using Two Ventricular Assist Devices: A Novel Operative Approach.

Increased use of continuous-flow left ventricular assist devices (LVADs) to treat advanced heart failure has heightened concern for right ventricular failure after LVAD implantation, which is associated with increased morbidity and mortality. Biventricular support is required in up to 30% of LVAD recipients. Currently, no durable long-term right ventricular assist device (RVAD) has been approved other than the Syncardia (Tucson, AZ) total artificial heart. A recent publication reported the placement of continuous flow LVAD in the heavily trabeculated right ventricle; however, this orientation may jeopardize both assist device and right ventricle function. We describe three cases of right-sided mechanical circulatory support with durable RVAD implanted in the right atrium, allowing long-term support with fewer anatomic limitations as compared with right ventricular cannulation.

QRS complex fragmentation and survival following left ventricular assist device implantation.

BACKGROUND: In patients with heart disease, the presence of a fragmented QRS complex (fQRS) on the surface electrocardiogram (ECG) is associated with an increased risk of mortality. We sought to evaluate the prevalence and location of fQRS before and after left ventricular assist device (LVAD) implantation and any associated risk of mortality. METHODS AND RESULTS: Twelve-lead surface ECGs before (pre-LVAD, n = 98) and after (early [< 7 days], n = 96, and late [≥ 30 days], n = 85, post-LVAD) LVAD implantation were evaluated for fQRS. Mortality data were gathered via review of medical records. The prevalence of fQRS increased significantly following LVAD implantation on early post-LVAD ECGs (31% to 47%, p < 0.01). Patients with fQRS in the anterior territory (precordial leads V1 to V5) on late post-LVAD ECGs had decreased survival or survival to cardiac transplantation over a 30 month follow-up period compared with patients who did not exhibit anterior fQRS (30% and 59%, respectively, p < 0.01). CONCLUSIONS: The prevalence of fragmented QRS on 12-lead ECG increases significantly in the anterior territory following LVAD implantation and is associated with decreased survival.

ICD lead parameters, performance, and adverse events following continuous-flow LVAD implantation.

BACKGROUND: Ventricular arrhythmias (VAs) in the months following continuous-flow left ventricular assist devices (LVADs) implantation are common and associated with increased morbidity and mortality. We sought to evaluate for changes in implantable cardioverter defibrillator (ICD) performance following LVAD implantation. METHODS: We retrospectively reviewed the ICD interrogation reports and medical records of patients who received a continuous-flow LVAD at the University of Chicago Medical Center between January 2008 and December 2010. Patients who did not have an ICD prior to LVAD implantation were excluded. RESULTS: Forty-four patients were included. Median right ventricular lead sensing amplitude decreased from 10.0 (interquartile range 7.6-13.6) mV prior to LVAD to 7.9 (5.9-9.3) mV after LVAD implantation (P < 0.01). Significant reductions in sensing threshold were associated with smaller lead diameters, smaller pace/sense electrode surface areas, and Medtronic ICD leads (Medtronic Inc., Minneapolis, MN, USA). Lead impedance and capture threshold did not change significantly. ICD-related adverse events occurred in 30% of patients and led to ICD modification in 18% of patients. CONCLUSIONS: Implantation of a continuous-flow LVAD is associated with changes in the performance of preexisting ICDs. ICD-related adverse events were encountered following LVAD implantation in this cohort, and at times resulted in invasive and noninvasive ICD system modification. Reductions in ICD sensing threshold after LVAD implantation may adversely affect ICD function. Formal ICD interrogation in addition to the regular follow-up testing is warranted post-LVAD.

Takotsubo cardiomyopathy after treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension is a fatal disease. Intravenous prostanoids are often utilized for long-term management of patients. The therapy requires a significant commitment and change in lifestyle for both the patient and family. Takotsubo cardiomyopathy, transient apical ballooning syndrome, has been reported in association with emotional and physical stress. This case report describes a patient with pulmonary arterial hypertension who developed Takotsubo cardiomyopathy after treatment initiation with intravenous treprostinil. Over time, the syndrome resolved and the patient had return of normal left ventricular function. Takotsubo cardiomyopathy should be recognized as a potential, rare complication of therapy initiation due to the severity of the illness and the emotional stress of the disease.

Dramatic improvement in hypoxemic respiratory failure after patent foramen ovale closure in a patient with obesity hypoventilation syndrome.

We report a case of a patient with pulmonary hypertension who presented with acute hypoxemic respiratory failure. The patient had continued refractory hypoxemia despite a prolonged ICU admission that included ventilatory support, and empiric therapy for pulmonary embolism and pneumonia. Transthoracic echocardiography (TTE) revealed a patent foramen ovale (PFO), which after percutaneous closure resulted in profound improvement in hypoxemia and clinical status.

The use of mechanical circulatory support as a bridge to transplantation in pediatric patients: an analysis of the United Network for Organ Sharing database.

OBJECTIVES: The use of mechanical circulatory support to bridge pediatric patients to cardiac transplantation presents unique challenges because of the difficult anatomy and physiology in these patients. METHODS: The United Network for Organ Sharing provided deidentifed patient-level data. The study population included 2532 transplantations performed on patients less than 19 years old in status 1/1A/1B between 1995 and 2005. Mechanical circulatory support was used in 431 patients: 241 (9.5%) received ventricular assist devices, 171 (6.8%) underwent extracorporeal membrane oxygenation, and 19 (0.8%) received intra-aortic balloon pumps. RESULTS: Patients supported on ventricular assist devices had similar levels of hospitalization and intensive care use and less need for inotropic support (P < .0002) than had those not needing support. Five- and 10-year posttransplantation survival was better in patients receiving ventricular assist devices and patients not receiving mechanical circulatory support than in patients receiving extracorporeal membrane oxygenation or intra-aortic balloon pumping (P < .0001). Among mechanically supported patients, patients with a body surface area of less than 0.30 (odds ratio, 1.70; 95% confidence interval, 1.18-2.43) and those requiring extracorporeal membrane oxygenation (odds ratio, 1.65; 95% confidence interval, 1.15-2.35) or intra-aortic balloon pumping (odds ratio, 1.91; 95% confidence interval, 1.02-3.56) had higher long-term mortality. The use of a ventricular assist device at transplantation did not predict higher long-term, posttransplantation mortality. CONCLUSIONS: Pediatric patients requiring a pretransplantation ventricular assist device have long-term survival similar to that of patients not receiving mechanical circulatory support. Early survival among patients undergoing extracorporeal membrane oxygenation and infants is poor, reinforcing the need for improvements in device design and physiologic management of infants and neonates.