Citations

Abstract Background A patent foramen ovale (PFO) is a persistent embryonic defect in the interatrial septum. Platypnoea-orthodeoxia syndrome is characterized by positional hypoxaemia that is most commonly due to right-to-left shunting through a PFO. Dynamic right-to-left shunting through a PFO can also exacerbate positional hypoxaemia without platypnea-orthodeoxia syndrome. Case summary A 78-year-old woman with hyperthyroidism and paroxysmal atrial fibrillation (AF) presented with positional hypoxaemia exacerbated by supine positioning. Diagnostic testing revealed intermittent right-to-left shunting through a PFO triggered by worsening atrial functional tricuspid regurgitation and elevated right atrial pressures. Diuresis, rate control, and thyroidectomy initially led to resolution of positional hypoxaemia, but recurrent AF episodes triggered right-to-left shunting with recurrent desaturation. Left atrial and cavo-tricuspid isthmus ablation led to restoration of normal sinus rhythm and resolution of positional hypoxaemia without PFO closure. Discussion The clinical presentation of intermittent intracardiac right-to-left shunting can mimic decompensated heart failure with pulmonary oedema. Persistent hypoxaemia out of proportion to the degree of pulmonary oedema and minimally responsive to supplemental O2 should raise suspicion for right-to-left shunt aetiology. Positional arterial blood gases can facilitate the diagnostic evaluation of refractory hypoxaemia in cases of suspected shunting. Diagnostic imaging for PFO detection includes both transthoracic and transesophageal echocardiography with Valsalva manoeuver and agitated saline injection. Closure of a PFO for management of arterial deoxygenation syndromes should not be performed before treating other causes of arterial deoxygenation and optimizing factors that may exacerbate shunting across the PFO.

Abstract Aims Obesity is a risk factor for heart failure with preserved ejection fraction (HFpEF), particularly in women, but the mechanisms remain unclear. The present study aimed to investigate the impact of central adiposity in patients with HFpEF and explore potential sex differences. Methods and results A total of 124 women and 105 men with HFpEF underwent invasive haemodynamic exercise testing and rest echocardiography. Central obesity was defined as a waist circumference (WC) ≥88 cm for women and ≥102 cm for men. Exercise‐normalized pulmonary capillary wedge pressure (PCWP) responses were evaluated by the ratio of PCWP to workload (PCWP/W) and after normalizing to body weight (PCWL). The prevalence of central obesity (77%) exceeded that of general obesity (62%) defined by body mass index ≥30 kg/m 2 . Compared to patients without central adiposity, patients with HFpEF and central obesity displayed greater prevalence of diabetes and dyslipidaemia, higher right and left heart filling pressures and pulmonary artery pressures during exertion, and more severely reduced aerobic capacity. Associations between WC and fasting glucose, low‐density lipoprotein (LDL) cholesterol, peak workload, and pulmonary artery pressures were observed in women but not in men with HFpEF. Although increased WC was associated with elevated PCWP in both sexes, the association with PCWP/W was observed in women but not in men. The strength of correlation between PCWP/W and WC was more robust in women with HFpEF as compared to men (Meng's test p = 0.0008), and a significant sex interaction was observed in the relationship between PCWL and WC ( p for interaction = 0.02). Conclusions Central obesity is even more common than general obesity in HFpEF, and there appear to be important sexual dimorphisms in its relationships with metabolic abnormalities and haemodynamic perturbations, with greater impact in women.

Background The aim of this study was to establish prognostic hemodynamic parameters in patients with mitral stenosis secondary to mitral annular calcification. Methods and Results A retrospective cohort of 105 patients undergoing transseptal catheterization for hemodynamic evaluation of mitral annular calcification–related mitral stenosis between 2004 and 2020 was studied. Mitral valve gradient (MVG) and mitral valve area (MVA; calculated by the Gorlin formula) were measured using direct left atrial and left ventricular pressures. The median age of the patients was 70.3 years (58.4–76.7 years), and 53.3% were women. The median MVA was 1.7 cm 2 (1.3–2.3 cm 2 ) and MVG was 7.3 mm Hg (5.3–10.3 mm Hg); left ventricular end‐diastolic pressure was 17.6±28.3 mm Hg. During a median of 2.1 years (0.7–4.5 years), there were 63 deaths; 1‐ and 5‐year survival were 76% and 40%, respectively. There was no association between left ventricular end‐diastolic pressure and survival. After adjusting for age and comorbidities, both MVA (hazard ratio [HR], 0.50 per cm 2 ; 95% CI, 0.34–0.73) and MVG (HR, 1.1 per mm Hg; 95% CI, 1.05–1.20) were independent predictors of death. Atrial fibrillation was also independently associated with mortality. When added to a combined model, MVA remained associated with death (HR, 0.51 per cm 2 ; 95% CI, 0.33–0.79) while MVG was not. Conclusions In patients with mitral annular calcification–related mitral stenosis, survival was poor. MVA and MVG were independently associated with death, but MVA was a better predictor of outcomes.

AbstractBackgroundMitral transcatheter edge‐to‐edge repair (MTEER) is an established therapeutic approach for mitral regurgitation (MR). Functional mitral regurgitation originating from atrial myopathy (A‐FMR) has been described.ObjectivesWe sought to assess the clinical, echocardiographic and hemodynamic considerations in A‐FMR patients undergoing MTEER.MethodsFrom 2014 to 2020, patients undergoing MTEER for degenerative MR (DMR), functional MR (FMR), and mixed MR were assessed. A‐FMR was defined by the presence of MR > moderate in severity; left ventricular (LV) ejection fraction (LVEF) ≥ 50%; and severe left atrial (LA) enlargement in the absence of LV dysfunction, leaflet pathology, or LV tethering. The diagnosis of A‐FMR (vs. ventricular‐FMR [V‐FMR]) was confirmed by three independent echocardiographers. Baseline characteristics, procedural outcomes as well as clinical and echocardiographic follow‐up are reported. Device success was defined as final MR grade ≤ moderate; MR reduction ≥1 grade; and final transmitral gradient <5 mmHg.Results306 patients underwent MTEER, including DMR (62%), FMR (19%), and mixed MR (19%). FMR cases included 37 (63.8%) V‐FMR and 21 (36.2%) A‐FMR. Tricuspid regurgitation (≥ moderate) was higher in A‐FMR (80.1%) compared to V‐FMR (54%) and DMR (42%). Device success did not significantly differ between A‐FMR and V‐FMR (57% vs. 73%, p = 0.34) or DMR (57% vs. 64%, p = 1.0). The A‐FMR cohort was less likely to achieve ≥3 grades of MR reduction compared to V‐FMR (19% vs. 54%, p = 0.01) and DMR (19% vs. 49.7%, p = 0.01). Patients with V‐FMR and DMR demonstrated significant reductions in mean left atrial pressure (LAP) and peak LA V‐wave, though A‐FMR did not (LAP −0.24 ± 4.9, p = 0.83; peak V‐wave −1.76 ± 9.1, p = 0.39). In follow‐up, echocardiographic and clinical outcomes were similar.ConclusionsIn patients undergoing MTEER, A‐FMR represents one‐third of FMR cases. A‐FMR demonstrates similar procedural success but blunted acute hemodynamic responses compared with DMR and V‐FMR following MTEER. Dedicated studies specifically considering A‐FMR are needed to discern the optimal therapeutic approaches.

Abstract Background and study aims In patients with inflammatory bowel disease (IBD), endoscopically visible lesions with distinct borders can be considered for endoscopic resection. The role of endoscopic submucosal dissection (ESD) for these lesions is not well defined because of a paucity of data. We aimed to evaluate the outcomes of colorectal ESD of dysplastic lesions in patients with IBD across centers in the United States. Patients and methods This was a retrospective analysis of consecutive patients with IBD who were referred for ESD of dysplastic colorectal lesions at nine centers. The primary endpoints were the rates of en bloc resection and complete (R0) resection. The secondary endpoints were the rates of adverse events and lesion recurrence. Results A total of 45 dysplastic lesions (median size 30mm, interquartile range [IQR] 23 to 42 mm) in 41 patients were included. Submucosal fibrosis was observed in 73 %. En bloc resection was achieved in 43 of 45 lesions (96 %) and R0 resection in 34 of 45 lesions (76 %). Intraprocedural perforation occurred in one patient (2.4 %) and was treated successfully with clip placement. Delayed bleeding occurred in four patients (9.8 %). No severe intraprocedural bleeding or delayed perforation occurred. During a median follow-up of 18 months (IQR 13 to 37 months), local recurrence occurred in one case (2.6 %). Metachronous lesions were identified in 11 patients (31 %). Conclusions ESD, when performed by experts, is safe and effective for large, dysplastic colorectal lesions in patients with IBD. Despite the high prevalence of submucosal fibrosis, en bloc resection was achieved in nearly all patients with IBD undergoing ESD. Careful endoscopic surveillance is necessary to monitor for local recurrence and metachronous lesions after ESD.

Abstract Aims Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in left heart disease (LHD). This study sought to characterize the pathophysiology of PVD across the spectrum of PH in LHD. Methods and results Patients with PH-LHD [mean pulmonary artery (PA) pressure &gt;20 mmHg and PA wedge pressure (PAWP) ≥15 mmHg] and controls free of PH or LHD underwent invasive haemodynamic exercise testing with simultaneous echocardiography, expired air and blood gas analysis, and lung ultrasound in a prospective study. Patients with PH-LHD were divided into isolated post-capillary PH (IpcPH) and PVD [combined post- and pre-capillary PH (CpcPH)] based upon pulmonary vascular resistance (PVR &lt;3.0 or ≥3.0 WU). As compared with controls (n = 69) and IpcPH-LHD (n = 55), participants with CpcPH-LHD (n = 40) displayed poorer left atrial function and more severe right ventricular (RV) dysfunction at rest. With exercise, patients with CpcPH-LHD displayed similar PAWP to IpcPH-LHD, but more severe RV–PA uncoupling, greater ventricular interaction, and more severe impairments in cardiac output, O2 delivery, and peak O2 consumption. Despite higher PVR, participants with CpcPH developed more severe lung congestion compared with both IpcPH-LHD and controls, which was associated lower arterial O2 tension, reduced alveolar ventilation, decreased pulmonary O2 diffusion, and greater ventilation-perfusion mismatch. Conclusions Pulmonary vascular disease in LHD is associated with a distinct pathophysiologic signature marked by greater exercise-induced lung congestion, arterial hypoxaemia, RV–PA uncoupling, ventricular interdependence, and impairment in O2 delivery, impairing aerobic capacity. Further study is required to identify novel treatments targeting the pulmonary vasculature in PH-LHD.

Aims Despite the common occurrence of coronary artery disease (CAD) and heart failure (HF) with preserved ejection fraction (HFpEF), there is limited evidence to guide revascularization. Methods and Results We investigated the long‐term outcomes of coronary artery bypass grafting (CABG) in patients with HF and significant CAD across the spectrum of ejection fraction, using a large national cohort of patients from the Veteran Affairs (VA) Medical Centers in the US. Patients with HF were stratified into groups, HFpEF, HF with mid‐range ejection fraction (HFmrEF), and HF with reduced ejection fraction (HFrEF) and compared to patients with no preoperative HF. We analysed 10 396 patients. Despite an increased hazard in the first year following revascularization, the long‐term survival (median follow‐up 6.6 years; interquartile range 3.7–10.1) of HFpEF post‐CABG was similar to controls (hazard ratio 0.85, 95% confidence interval 0.68‐1.06), but survival progressively declined with HFmrEF and HFrEF. Similar trends were seen with recurrent HF hospitalization with lower risk with baseline HFpEF (43.9 ± 6.9/100 patient‐years) compared to HFmrEF (65.9 ± 3.8/100 patient‐years) and HFrEF (93.4 ± 4.8/100 patient‐years). Although HFpEF patients had lower mortality and HF hospitalization post‐CABG compared to patients with a lower ejection fraction, they experienced the highest rates of future myocardial infarction. Conclusion Although HFpEF patients with CAD have greater short‐term risk post‐CABG, their long‐term survival is comparable to controls. However, they are at increased risk for HF hospitalizations and myocardial infarction. These data support the safety of CABG in HFpEF patients and suggest continuum of mortality risk for ischaemic HF when stratified by baseline ejection fraction before revascularization.

Abstract Background A substantial proportion of patients with heart failure (HF) with preserved ejection fraction (HFpEF) present with normal natriuretic peptide (NP) levels. The pathophysiology and natural history for this phenotype remain unclear. Methods and results Consecutive subjects undergoing invasive cardiopulmonary exercise testing for unexplained dyspnoea at Mayo Clinic in 2006–18 were studied. Heart failure with preserved ejection fraction was defined as a pulmonary arterial wedge pressure (PAWP) ≥15 mmHg (rest) or ≥25 mmHg (exercise). Patients with HFpEF and normal NP [N-terminal of the pro-hormone B-type natriuretic peptide (NT-proBNP) &lt; 125 ng/L] were compared with HFpEF with high NP (NT-proBNP ≥ 125 ng/L) and controls with normal haemodynamics. Patients with HFpEF and normal (n = 157) vs. high NP (n = 263) were younger, yet older than controls (n = 161), with an intermediate comorbidity profile. Normal NP HFpEF was associated with more left ventricular hypertrophy and worse diastolic function compared with controls, but better diastolic function, lower left atrial volumes, superior right ventricular function, and less mitral/tricuspid regurgitation compared with high NP HFpEF. Cardiac output (CO) reserve with exercise was preserved in normal NP HFpEF [101% predicted, interquartile range (IQR): 75–124%], but this was achieved only at the cost of higher left ventricular transmural pressure (LVTMP) (14 ± 6 mmHg vs. 7 ± 4 mmHg in controls, P &lt; 0.001). In contrast, CO reserve was decreased in high NP HFpEF (85% predicted, IQR: 59–109%), with lower LVTMP (10 ± 8 mmHg) compared with normal NP HFpEF (P &lt; 0.001), despite similar PAWP. Patients with high NP HFpEF displayed the highest event rates, but normal NP HFpEF still had 2.7-fold higher risk for mortality or HF readmissions compared with controls (hazard ratio: 2.74, 95% confidence interval: 1.02–7.32) after adjusting for age, sex, and body mass index. Conclusion Patients with HFpEF and normal NP display mild diastolic dysfunction and preserved CO reserve during exercise, despite marked elevation in filling pressures. While clinical outcomes are not as poor compared with patients with high NP, patients with normal NP HFpEF exhibit increased risk of death or HF readmissions compared with patients without HF, emphasizing the importance of this phenotype.

Abstract Aims Pulmonary hypertension (PH) has been consistently associated with adverse outcomes in hospitalized patients. Limited epidemiologic data exist regarding PH in the cardiac intensive care unit (CICU) population. Here, we describe the prevalence, aetiology, and outcomes of PH in the CICU. Methods and results Cardiac intensive care unit patients admitted from 2007 to 2018 who had right ventricular systolic pressure (RVSP) measured via transthoracic echocardiography near CICU admission were included. PH was defined as RVSP &gt;35 mmHg, and moderate-to-severe PH as RVSP ≥50 mmHg. Predictors of in-hospital mortality were determined using multivariable logistic regression. Among 5042 patients (mean age 69.4 ± 14.8 years; 41% females), PH was present in 3085 (61%). The majority (68%) of patients with PH had left heart failure, and 29% had lung disease. In-hospital mortality occurred in 8.3% and was more frequent in patients with PH [10.9% vs. 4.2%, adjusted odds ratio (OR) 1.40, 95% confidence interval (CI) 1.03–1.92, P = 0.03], particularly patients with moderate-to-severe PH (14.4% vs. 6.2%, adjusted OR 1.65, 95% CI 1.27–2.14, P &lt; 0.001). In-hospital mortality increased incrementally as a function of higher RVSP (adjusted 1.18 per 10 mmHg increase, 95% CI 1.09–1.28, P &lt; 0.001). Patients with higher RVSP or moderate-to-severe PH had increased in-hospital mortality across admission diagnoses (all P &lt; 0.05). Conclusions Pulmonary hypertension is very common in the CICU population and appears to be independently associated with a higher risk of death during hospitalization, although the strength of this association varies according to the underlying admission diagnosis. These data highlight the importance of PH in patients with cardiac critical illness.