Jokhadar, Maan

Background The purpose of this study was to assess the clinical benefits of guideline‐directed medical therapy (GDMT) for heart failure (HF) in adults with congenital heart disease and HF with reduced ejection fraction. Methods HF with reduced ejection fraction was defined as stage B/C HF and systemic left ventricular ejection fraction <50%. GDMT score was assessed at baseline encounter (baseline GDMT score) and 1‐year follow‐up. GDMT uptitration was calculated as defined as ∆GDMT score from baseline. Cox regression was used to assess the relationship between HF therapy (baseline and ∆GDMT score) and outcomes (HF hospitalization and mortality). Results Of 778 patients (age 44±16, 480 [62%] males), baseline GDMT score was 2 (1, 3) and ∆GDMT score was 0.62 (95% CI, 0.55–0.69). Of 778, only 258 (33%) had GDMT uptitration (∆GDMT score >0). Higher use of GDMT at baseline (adjusted HR per 1 point increase in GDMT score 0.81, 95% CI, 0.74–0.88, P <0.001), and increased use of GDMT over time (adjusted HR for 1 point increase in ∆GDMT score HR 0.70, 95% CI, 0.61–0.79, P <0.001) were associated with lower risk of HF hospitalization. Higher baseline GDMT score (adjusted HR 0.85, 95% CI, 0.76–0.94, P <0.001), and ∆ GDMT score (adjusted HR 0.82, 95% CI, 0.71–0.94, P <0.000) were also associated with lower mortality. Conclusions GDMT use at baseline and GDMT uptitration were associated with improved outcomes and suggest a dose‐dependent relationship between use of GDMT and risk of adverse outcomes. Furthermore, 67% of patients did not receive GDMT uptitration, suggesting suboptimal therapy, and opportunities for improvement.

Abstract Aims Echo-derived left atrial (LA) stiffness index improves prognostication in patients with heart failure preserved ejection fraction but has not been studied in adults with repaired coarctation of aorta (COA). We hypothesized that, among adults with COA, those with high LA stiffness index would have worse disease severity indices [peak VO2, NT-proBNP, and right ventricular to pulmonary artery (RV-PA) coupling], heart failure hospitalization, and all-cause mortality. Methods and results LA stiffness index was estimated using the baseline echocardiogram as the quotient of septal E/e′ and LA reservoir strain (E/e′/LARS). Using the median septal LA stiffness index as the cut-off, patients were divided into high LA stiffness index (LA stiffness index &gt;0.28) vs. low LA stiffness index groups (LA suggests index ≤0.28). The study comprised of 729 patients [age 36 ± 16 years; males 437 (60%)]. LA stiffness index correlated with RV-PA coupling (r = −0.56, P &lt; 0.001), NT-proBNP (r = 0.62, P &lt; 0.001), and predicted peak VO2 (r = −0.51, P &lt; 0.001). High LA stiffness index was associated with heart failure hospitalization (adjusted HR 3.17, 95% confidence interval (CI) 1.84–7.36, P = 0.007) and all-cause mortality (adjusted HR 2.81, 95% CI 1.28–12.32, P = 0.005). LA stiffness index had superior prognostic performance for predicting 5-year risk of heart failure hospitalization (AUC 0.803, 95% CI 0.756–0.849, P &lt; 0.001) and all-cause mortality (AUC 0.786, 95% CI 0.742–08.30, P &lt; 0.001) compared with conventional echocardiographic indices of left heart diastolic function. Conclusion LA stiffness index improves prognostication in adults with COA and can potentially be used to guide timing of intervention or monitor response to therapy.

Background Patients with cardiohepatic syndrome are at higher risk of adverse outcomes in the cardiac intensive care unit. We hypothesized that cardiohepatic syndrome phenotypes would exhibit differences in their clinical and transthoracic echocardiogram hemodynamic profiles, portending a higher risk of mortality. Methods We included unique CICU patients with an admission diagnosis of heart failure from 2007 to 2018 with available data for 1 or more admission liver function tests. Echocardiographic variables were extracted from patients who had a transthoracic echocardiogram within 1 day of admission. We assigned patients to 1 of 4 mutually exclusive cardiohepatic syndrome phenotype groups: normal, hepatocellular, cholestasis, and combined. Results We included 3992 CICU patients; 2483 had an available transthoracic echocardiogram. Patients with cholestasis had more right ventricular systolic dysfunction and congestion, whereas those with hepatocellular injury had more left ventricular systolic dysfunction and poor forward flow; hemodynamics and biventricular function were worst in the combined group. In‐hospital mortality occurred in 14.6% and was higher for patients with cholestasis or hepatocellular injury, especially those with greater extent/severity and worse biventricular function or poor hemodynamics. After adjustment, only the group with hepatocellular injury (adjusted odds ratio [OR], 1.35 [95% CI, 1.04–1.75], P =0.03) and the combined group (adjusted OR, 1.75 [95% CI, 1.30–2.34], P <0.001) remained at higher risk. One‐year mortality was highest in the combined group (adjusted hazard ratio [HR], 1.29 [95% CI, 1.10–1.51], P =0.002). Conclusions Cardiohepatic syndrome phenotypes are associated with distinct echocardiographic profiles. Patients with the combined cardiohepatic syndrome phenotype were at highest risk of mortality, particularly if this was combined with poor cardiac function.

Abstract Aims Systemic ventricular (SV) strain imaging improves early detection of systolic dysfunction in patients with congenital heart disease and biventricular circulation. However, its role for risk stratification in the Fontan population has not been systematically studied. We hypothesized that among Fontan patients with normal SV ejection fraction (Echo_EF) at baseline, those with reduced SV longitudinal strain (Echo_LS) would have a higher risk of progressive SV systolic dysfunction, greater neurohormonal activation, and cardiovascular events (heart failure hospitalization/death/transplant) during follow-up. Methods and results We studied adults with Fontan palliation and normal SV systolic function (Echo_EF &gt;50%) at baseline who underwent follow-up echocardiogram &gt;36 months after the baseline echocardiogram. Echo_LS was assessed from the apical 4-chamber window using speckle tracking echocardiography. Patients were divided into reduced vs. normal Echo_LS groups, using −18% as the cut-off point. Echo_LS, Echo_EF, and NT-proBNP were assessed at baseline and follow-up encounters. Of 272 patients (age, 28 ± 8 years), 98 (36%) and 174 (64%) had reduced vs. normal Echo_LS. The reduced_Echo_LS group had progressive SV systolic dysfunction [worse temporal decline in Echo_EF (relative_Δ_Echo_EF −12.8% vs. −2.1%, P &lt; 0.001)], and higher prevalence of new-onset SV systolic dysfunction [30% (29/98) vs. 8% (13/174), P &lt; 0.001]. The reduced Echo_LS group also had greater neurohormonal activation [relative Δ_ NT-proBNP 36 (95%CI, 27–43) % vs. 17 (95%CI, 11–23) %, P &lt; 0.001], and higher risk of cardiovascular events (adjusted hazard ratio 1.84, P = 0.009). Conclusion Echo_LS improves risk stratification in Fontan patients with normal Echo_EF and may provide an opportunity for early interventions to improve outcomes.

Abstract INTRODUCTION: Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis (PVOD/PCH) is a rare subgroup of pulmonary arterial hypertension (PAH). Unfortunately, there is significant overlap between PVOD and PAH, making differentiation difficult. Thus, a constellation of investigations is necessary to suggest such a diagnosis. CASE PRESENTATION: A 65-year-old female with a history of smoking was diagnosed with idiopathic PAH following 2 months of worsening dyspnea. Right heart catheterization (RHC) revealed a mean PA pressure (mPAP) 58mmHg, pulmonary artery wedge pressure (PAWP) 14mmHg, cardiac output/index (CO/CI) 5.5/2.6, and pulmonary vascular resistance (PVR) 8 Wood units. Further workup excluded other causes of pulmonary hypertension (Table 1). Tadalafil was initially started followed by macitentan, which were associated with worsening hypoxemia and dyspnea. Computed tomography (CT) scan of the chest revealed mediastinal lymphadenopathy and small bilateral pleural effusions. This development in relation to the initiation of PAH-directed therapies raised concern for possible PVOD. Medical therapy was downtitrated, but worsening hypoxemia in the setting of worsening edema led to the cessation of all therapies. Due to clinical concern, the patient was admitted for a repeat RHC and close supervision during a trial of epoprostenol. RHC revealed a mPAP of 57mmHg, PAWP 5mmHg, CO/CI 3.4/1.6 and PVR 15 Wood units. She had been on metoprolol for hypertension which was discontinued. Low-dose epoprostenol was started at 1ng/kg/min. Her oxygen requirements increased slightly which improved with diuresis. Epoprostenol was slowly titrated with improvements in CI. Repeat chest CT showed mild diffuse centrilobular nodular opacities more prominent compared to prior scans, and adenopathy. After a steady dose of epoprostenol (4ng/kg/min), the patient improved with lower oxygen requirements. She was discharged with plans to continue low dose outpatient epoprostenol and start sotatercept. Lung transplant evaluation is on hold pending response to this approach. Genetic testing is pending. DISCUSSION: Despite challenges of definitive diagnosis where lung biopsy is risky, a diagnosis of PVOD can be supported from a spectrum of strongly suggestive clinical, hemodynamic and radiographic features. Though genetic testing for the EIF2AK4 mutation may confirm the presence of heritable PVOD, its absence does not exclude its possibility as most cases do not have an identifiable genetic cause. Management is challenging given ineffective or potentially harmful responses to PAH-directed therapies, though some do respond to a variable extent. As suggested here, close supervision during epoprostenol infusion adds to the limited body of evidence supporting such endeavors when initiating vasodilatory therapies in patients with suspected PVOD.

BACKGROUND: Bioprosthetic valve dysfunction and reoperations/reinterventions are common after aortic valve replacement (AVR) with bioprosthetic valves, leading to cycles of left ventricular (LV) pressure overload and unloading. The purpose of this study was to compare postoperative changes in LV structure and function and their relationship to clinical outcomes in young patients who underwent AVR with bioprosthetic valves (Bio_AVR group) versus mechanical prosthetic valves (Mech_AVR group). METHODS: Retrospective study of adults with congenital heart disease who underwent AVR at Mayo Clinic (2003–2023). The Bio_AVR group was matched 1:2 to the Mech_AVR group. LV indices (LV mass index, relative wall thickness, LV global longitudinal strain, averaged e′, and averaged E/e′) and clinical indices (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and New York Heart Association class) were assessed preoperatively, and at 1, 5, and 10 years post-AVR. RESULTS: We studied 151 and 302 patients in the Bio_AVR and Mech_AVR groups, respectively (age 38±16 years, 58% males). Both groups had similar LV and clinical indices at baseline and 1 year post-AVR. However, the Bio_AVR group had higher LV mass index, relative wall thickness, and averaged E/e′, and lower averaged e′ and LV global longitudinal strain at 5 and 10 years post-AVR. Of 51 patients from the Bio_AVR group who underwent a second AVR, there was less robust improvement in LV indices and clinical indices after the second AVR compared with the first AVR. CONCLUSIONS: AVR with a bioprosthetic valve was associated with progressive LV hypertrophy and dysfunction, and worsening clinical status compared with mechanical prosthetic valves. This provides further evidence against the use of bioprosthetic AVR in young patients.