A Nomogram for Predicting 3-Year Mortality in Patients with Pulmonary Hypertension due to Left Heart Failure: A Retrospective Analysis of a Prospective Registry Study.

INTRODUCTION: Pulmonary hypertension due to left heart failure (PH-LHF) is a disease with high prevalence and 3-year mortality rates. Consequently, timely identification of patients with high mortality risk is critical. This study aimed to build a nomogram for predicting 3-year mortality and screening high-risk PH-LHF patients. METHODS: This nomogram was developed on a training cohort of 175 patients with PH-LHF diagnosed by right heart catheterization. Multivariate Cox regression was used to identify independent predictors and develop this nomogram. The median total points obtained from the nomogram were used as a cutoff point, and patients were classified into low- and high-risk groups. The concordance index (C-index) and calibration curve were utilized to ascertain the predictive accuracy and discriminative ability of the nomogram. External validation was performed using a validation cohort of 77 PH-LHF patients from other centers. RESULTS: Multivariate Cox regression showed that the New York Heart Association Functional classification (NYHA FC), uric acid level, and mean pulmonary arterial pressure were all independent predictors and incorporated into the nomogram. The nomogram showed good discrimination (C-index of 0.756; 95% CI: 0.688-0.854) and good calibration. The Kaplan-Meier survival analysis showed that patients in the high-risk group had worse survival (p < 0.001). In the external validation, the nomogram showed both good discrimination (C-index of 0.738; 95% CI: 0.591-0.846) and calibration. CONCLUSION: The nomogram had a good performance in predicting 3-year mortality and can effectively identify high-risk patients. The nomogram may help to reduce the mortality of PH-LHF.

A study of the efficacy of sacubitril/valsartan plus dapagliflozin combination treatment in pulmonary arterial hypertension due to left heart disease.

OBJECTIVE: To determine the efficacy of sacubitril/valsartan plus dapagliflozin in the treatment of patients with pulmonary arterial hypertension (PAH) due to left heart disease and to explore new treatment regimen for PAH due to left heart disease. METHODS: This study is a randomized controlled trial (RCT) study of 120 patients with PAH due to left heart disease admitted to the cardiovascular department of our hospital from Dec. 2019 to Dec. 2021. The patients were randomized 1:1 to the study group and control group. All patients were given baseline treatments targeting left heart disease and symptoms of PAH. In addition to the baseline treatments, patients in the control group were given sacubitril/valsartan tablets, while patients in the study group were given sacubitril/valsartan tablets plus dapagliflozin tablets. After 6 months of treatment, parameters including left heart function and exercise tolerance, Hemodynamics (left ventricular end systolic diameter [LVSED], left ventricular end diastolic diameter [LVEDD], left ventricular ejection fraction [LVEF], 6 min walk distance (6MWD), mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP)), vascular endothelial function (plasma endothelin (ET) -1 and nitric oxide [NO]), heart failure markers (plasma N-terminal pro-brain natriuretic peptide (NT-proBNP)], inflammatory factors (serum C reactive protein [CRP], interleukin (IL)-6, and tumor necrosis factor (TNF)-α], and adverse drug reactions (ADRs) were assessed in both groups. RESULTS: Both groups had reduced LVESD and LVEDD, increased LVEF, and extended 6MWD after 6 months of treatment. The improvements in these parameters were significantly greater in the study group than in the control group (all P < 0.05). In addition, both the mPAP and PASP showed a decrease, and the mPAP and PASP in the study group were lower than those in the control group (p<0.05). Furthermore, both groups had decreased plasma ET-1 and NT-proBNP but increased plasma NO after 6 months of treatment. The improvements in these parameters were significantly greater in the study group than in the control group (all P < 0.05). Serum CRP, IL-6 and TNF-α levels were decreased in both groups after 6 months of treatment, and were significantly lower in the study group than in the control group (all P < 0.05). There was no significant difference in the overall incidence of ADRs between the two groups (P > 0.05). CONCLUSION: Sacubitril/valsartan plus dapagliflozin in the treatment with PAH due to left heart disease can improve left heart function of patients by improving vascular endothelial functions and alleviating inflammation, which helps to reduce the PAH process. Therefore, this combination treatment is safe and effective in PAH due to left heart disease.

How Would the Authors Treat Their Own Temporary Left Ventricular Failure With Mechanical Circulatory Support?

In the last 20 years, mechanical circulatory supports (MCS) have overturned completely the outcomes and the clinical recovery of patients with isolated acute left ventricle failure (iALVF). This usually occurs more frequently than right-sided heart failure or biventricular dysfunction, and it mainly is caused by acute myocardial infarction. The primary role of MCS is to restore the tissue metabolism to preserve the vital organs' function but, on the other hand, they also have to relieve the workload stress on the heart. In this way, they allow not only the heart to recover from the acute event, but MCS also can stabilize the patient toward cardiac transplantation. The short-term MCS devices currently used in clinical practice are the intraaortic balloon pump, the Impella (Abiomed, Danvers, MA), and venoarterial extracorporeal membrane oxygenation (VA-ECMO), but the choice of the right and tailored device for each patient, as well as the timing to use it, is actually one of the most debated topics of MCS management.

Outflow cannula position for left ventricular assist device: A propensity score-matched study.

OBJECTIVE: The clinical consequences of alternative outflow cannula positioning in patients undergoing left ventricular assist device implantation are unknown. We evaluated clinical outcomes in patients who underwent implantation with the outflow cannula implanted from the right side into the ascending aorta versus the left side of the pericardium. METHODS: Fifty consecutive patients with terminal left heart failure underwent implantation using the Medtronic Heartware Ventricular Assist Device at Toronto General Hospital. Patients were divided between left and right outflow cannula positioning during implantation where anastomosis occurred in the ascending aorta. Propensity score matching using exact matching on the following pre-specified covariates: Interagency Registry for Mechanically Assisted Circulatory Support score, previous cardiac surgery, and preoperative inotrope use. RESULTS: Fifty consecutive patients (25 left implantation and 25 right implantation) were included in the unmatched cohort and 45 patients (25 left implantation and 20 right implantation) were included in the matched cohort. No significant differences in baseline demographics. Pump thrombosis occurred in 10% (n = 2) receiving right-sided implantation and 8% (n = 2) with left implantation (p = 1.00). Postoperative stroke occurred in 10% (2/20) with right implantation and 16% (4/25) with left implantation (p = .88). No difference in 1-year mortality between right 20% (5/25) and left 25% (5/20) implantation (p = .97). CONCLUSION: No observed difference in mortality when adjusting for competing risk of heart transplantation. There was also no difference in stroke, pump thrombosis, driveline infection. Larger studies are required to confirm these findings. These preliminary data support the use of left-sided anastomoses to facilitate subsequent re-entry during heart transplantation.

Impact of ß-blocker therapy on right ventricular function in heart failure patients with reduced ejection fraction. A prospective evaluation.

BACKGROUND: Beta-blocker (ß-blocker) therapy has been shown to improve mortality and reduce hospitalizations in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Although the physiological action mechanisms of ß-blockers are well described, their effects on right ventricular (RV) function have not been prospectively studied. OBJECTIVE: This prospective study aimed to (a) evaluate whether ß-blocker therapy impacts RV remodeling based on echo parameters and (b) determine the predictive echo factors of ß-blocker therapy response. METHODS: From September 2017 to September 2018, HF patients were prospectively enrolled using CIBIS criteria: Class II, III, or IV HF; left ventricular ejection fraction (LVEF) of ≤40%; hospitalized for HF within the previous 12 months. Echo evaluation was performed before initiating ß-blocker therapy and 3 months after optimal dose adjustment. Based on previous studies, patients with (absolute) LVEF ≥ 5% improvement were considered significant ß-blocker therapy responders. RESULTS: Overall, 40 patients (pts) completed the study, characterized as follows by age: 70 ± 10 years; gender: 10 women; cardiomyopathy etiology: idiopathic in 24 and ischemic in 16; NYHA Class: II in 22 and III in 10; LVEF: 32 ± 5%; and NTProBNP: 2665 ± 2400 pg/mL. The final population comprised 32 pts (79%), with eight (21%) excluded: two because of ß-blocker therapy intolerance, one lost to follow-up, and five withdrew from the study. Under ß-blocker therapy, several echo parameters significantly improved: LVEF from 31.7 ± 9 to 40.5 ± 9 (P < .0001); LV end-diastolic volume (EDV) from 154 ± 54 to 143 ± 45 mL (P = .06); LV end-systolic volume (ESV) from 107 ± 49 to 88 ± 37 mL (P = .0006); LV ES from 46 ± 11 to 64 ± 13 mL (P = .008); LV end-diastolic diameter (EDD) from 57 ± 9 to 54 ± 6 mm (P = .04); LV end-systolic diameter (ESD) from 48 ± 10 to 44 ± 7 mm (P = .007); and right ventricular systolic pressure (RV SP) from 39 ± 10 to 32 ± 8 mm Hg (P = .0001). Significant modifications were observed in terms of RV echo parameters: right ventricular (RV) size decreased from 30 ± 4 to 27 ± 5 mm (P = .03), while RV systolic function significantly improved based on tricuspid annular plane systolic excursion (TAPSE) (16.5 ± 4 vs. 19 ± 4 mm; 0.0006); DTI-derived tricuspid lateral annular systolic velocity wave (S') (10 ± 2 vs. 11.3 ± 3 cm/s; P = .03); and RIMP (Tei index) (0.5 ± 0.1 vs 0.46 ± 0.1; P = .04). RV 2D fractional area change (%) did not significantly differ despite a clear improvement tendency (35 ± 6 vs. 37 ± 4%; P = .1). No significant modifications were observed concerning LV diastolic parameters. Overall, ß-blocker echo responders (n = 23/32; 72%) exhibited the same left and right echo parameters. No echo variables predicted the ß-blocker response. CONCLUSIONS: In HFrEF pts, ß-blocker therapy significantly improves LV and RV systolic remodeling. Accordingly, ß-blocker therapy could be applied as soon as possible in HFrEF patients with right ventricular dysfunction so as to limit RV remodeling.

Surgical and physiological challenges in the development of left and right heart failure in rat models.

Rodent surgical animal models of heart failure (HF) are critically important for understanding the proof of principle of the cellular alterations underlying the development of the disease as well as evaluating therapeutics. Robust, reproducible rodent models are a prerequisite to the development of pharmacological and molecular strategies for the treatment of HF in patients. Due to the absence of standardized guidelines regarding surgical technique and clear criteria for HF progression in rats, objectivity is compromised. Scientific publications in rats rarely fully disclose the actual surgical details, and technical and physiological challenges. This lack of reporting is one of the main reasons that the outcomes specified in similar studies are highly variable and associated with unnecessary loss of animals, compromising scientific assessment. This review details rat circulatory and coronary arteries anatomy, the surgical details of rat models that recreate the HF phenotype of myocardial infarction, ischemia/reperfusion, left and right ventricular pressure, and volume overload states, and summarizes the technical and physiological challenges of creating HF. The purpose of this article is to help investigators understand the underlying issues of current HF models in order to reduce variable results and ensure successful, reproducible models of HF.

EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond.

These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/PSPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/PSPECT an essential method for the diagnosis of PE. When V/PSPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/PSPECT interpretation are discussed. In conclusion, V/PSPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.

Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of L-arginine than patients with LVSD (p < 0.05). L-Arginine correlated to 6 min walking distance (6MWD) (r s = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

Treatment and Prognosis of Pulmonary Hypertension in the Left Ventricular Assist Device Patient.

This review will discuss the medical management of pulmonary hypertension in patients with left ventricular assist devices. Although much has been written on the management of primary pulmonary hypertension, also called pulmonary arterial hypertension, this review will instead focus on the treatment of pulmonary hypertension secondary to left heart disease. The relevant pharmacotherapy can be divided into medications for treating heart failure, such as diuretics and ß-blockers, and medications for treating pulmonary hypertension. We also discuss important preoperative considerations in patients with pulmonary hypertension; the relationships between left ventricular assist devices, pulmonary hemodynamics, and right heart failure; as well as optimal perioperative and long-term postoperative medical management of pulmonary hypertension.

Outcomes in World Health Organization group II pulmonary hypertension: mortality and readmission trends with systolic and preserved ejection fraction-induced pulmonary hypertension.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has been increasingly recognized as a leading cause of pulmonary hypertension (HFpEF-PH). It remains unknown how HFpEF-PH fares in relation to systolic HF (reduced ejection fraction)-induced PH (HFrEF-PH). Therefore, we sought to determine the long-term morbidity and mortality of HFpEF-PH and HFrEF-PH. METHODS AND RESULTS: We studied all patients over a 6-year period with symptomatic HF and severe PH (PASP ≥65 mm Hg) in The Bronx, New York. We classified patients as having either preserved (≥50%) or reduced (≤35%) left ventricular ejection fraction. Trends in mortality and HF readmission rates were defined in 650 patients (HFrEF-PH: n = 277; HFpEF-PH: n = 373). HFpEF-PH patients were older and more often female and white. HFrEF-PH patients were more often black, had ischemic cardiomyopathy, and were on typical HF drug regimens. Patients with HFpEF-PH had a significantly increased all-cause 5-year mortality (52% vs 42%; P = .024). HFpEF-PH was a significant predictor of mortality (adjusted hazard ratio 1.70; P = .012). Patients with HFrEF-PH had more HF readmissions (≥1) than patients with HFpEF-PH (28.6% vs 15%; P = .003), especially within the 1st year (9.1% vs 1.7%; P = .005). CONCLUSIONS: Patients with HFrEF-PH and HFpEF-PH have a significantly elevated long-term mortality, with HFpEF-PH having a higher 5-year mortality rate. These findings testify to the overall poor prognosis of World Health Organization Group II PH, especially HFpEF-PH.

Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease.

Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries.

Cardiopulmonary interactions in left heart failure.

The primary impact of ventilation and ventilatory efforts on left ventricular (LV) function in left ventricular dysfunction relate to how changes in intrathoracic pressure (ITP) alter the pressure gradients for venous return into the chest and LV ejection out of the chest. Spontaneous inspiratory efforts by decreasing ITP increase both of these pressure gradients increasing venous blood flow and impeding LV ejection resulting in increased intrathoracic blood volume. In severe heart failure states when lung compliance is reduced, or airway resistance is increased these negative swings in ITP can be exacerbated leading to LV failure and acute cardiogenic pulmonary edema. By merely reversing these negative swings in ITP by the use of non-invasive continuous positive airway pressure (CPAP), these profoundly detrimental forces can be immediately reversed, and cardiovascular stability can be restored in moments. This forms the clinical rationale for the immediate use of CPAP for the treatment of acute cardiogenic pulmonary edema. Increasing ITP during positive pressure ventilation decreases the pressure gradients for venous return and LV ejection decreasing intrathoracic blood volume. In a hypovolemic patient even with LV dysfunction this can result in hypotension due to inadequate LV preload. Minor increases in ITP as occur using pressure-limited positive-pressure ventilation primarily reverse the increased LV afterload of negative swings in ITP and if fluid overload was already present, minimally alter cardiac output. The effect of changes in lung volume on LV function are related primarily to its effects on right ventricular (RV) function through changes in pulmonary vascular resistance and overdistention (hyperinflation). In acute lung injury with alveolar collapse, positive pressure ventilation may reduce pulmonary vascular resistance if alveolar recruitment predominates. Hyperinflation, however, impedes diastolic filling while simultaneously increasing pulmonary vascular resistance. Thus, increasing lung volume can reduce RV afterload by reversing hypoxic pulmonary vasoconstriction or increase afterload by overdistention. Hyperinflation can also impede RV filling. All of these processes can be readily identified at the bedside using echocardiography.

Biomechanical and Mechanobiological Drivers of the Transition From PostCapillary Pulmonary Hypertension to Combined Pre-/PostCapillary Pulmonary Hypertension.

Combined pre-/postcapillary pulmonary hypertension (Cpc-PH), a complication of left heart failure, is associated with higher mortality rates than isolated postcapillary pulmonary hypertension alone. Currently, knowledge gaps persist on the mechanisms responsible for the progression of isolated postcapillary pulmonary hypertension (Ipc-PH) to Cpc-PH. Here, we review the biomechanical and mechanobiological impact of left heart failure on pulmonary circulation, including mechanotransduction of these pathological forces, which lead to altered biological signaling and detrimental remodeling, driving the progression to Cpc-PH. We focus on pathologically increased cyclic stretch and decreased wall shear stress; mechanotransduction by endothelial cells, smooth muscle cells, and pulmonary arterial fibroblasts; and signaling-stimulated remodeling of the pulmonary veins, capillaries, and arteries that propel the transition from Ipc-PH to Cpc-PH. Identifying biomechanical and mechanobiological mechanisms of Cpc-PH progression may highlight potential pharmacologic avenues to prevent right heart failure and subsequent mortality.

Effect of different pre-hospital first aid methods on the efficacy and prognosis of acute myocardial infarction with left heart failure: a systematic review and meta-analysis.

Background: Pre-hospital first aid for acute myocardial infarction (AMI) is an important way to save patients. However, there are still some disputes about the way of pre-hospital first aid. Therefore, this paper provides a Meta-analysis to evaluate the efficacy and prognosis of different prehospital care for AMI with left heart failure. Methods: By searching the published studies in the databases, the literature related to the pre-hospital first aid for patients with AMI and left heart failure was screened out. The quality of the literature was evaluated according to the Newcastle-Ottawa scale (NOS), and the corresponding data were extracted for meta-analysis. Meta-analysis was performed on 7 outcome indicators (clinical effect of patients after treatment, respiratory rate, heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), survival status, and incidence of complications). A funnel plot and Egger's test were used to test risk of bias. Results: A total of 16 articles were finally included, comprising a total of 1,465 patients. The literature quality evaluation found that 8 literatures were rated as low risk of bias, and 8 literatures were rated as medium risk of bias. The meta-analysis results showed that the clinical effect of the first aid and then transportation group was better than that of the transportation and then first aid group [risk ratio (RR) =1.35, 95% confidence interval (CI): 1.27 to 1.45, P<0.01]; the respiratory rate decreased [mean difference (MD) =-4.84, 95% CI: -6.50 to -3.18, P<0.01]; the heart rate decreased (MD =-11.34, 95% CI: -12.69 to -9.99, P<0.01); SBP decreased (MD =-6.00, 95% CI: -10.00 to -2.00, P<0.01); the DBP decreased (MD =-3.54, 95% CI: -4.45 to -2.64, P<0.01); the survival status of the patients improved (RR =1.29, 95% CI: 1.18 to 1.41, P<0.01); the incidence of complications was reduced (RR =0.31, 95% CI: 0.20 to 0.48, P<0.01). Conclusions: Pre-hospital first aid and then transportation can significantly improve the clinical treatment effect of patients. However, considering that the literatures included in this paper are non-randomized controlled studies and the overall quality of the included literatures is not high and the number of studies is limited, further exploration is needed.

The emerging role of sacubitril/valsartan in pulmonary hypertension with heart failure.

Pulmonary hypertension due to left heart disease (PH-LHD) represents approximately 65%-80% of all patients with PH. The progression, prognosis, and mortality of individuals with left heart failure (LHF) are significantly influenced by PH and right ventricular (RV) dysfunction. Consequently, cardiologists should devote ample attention to the interplay between HF and PH. Patients with PH and HF may not receive optimal benefits from the therapeutic effects of prostaglandins, endothelin receptor antagonists, or phosphodiesterase inhibitors, which are specific drugs for pulmonary arterial hypertension (PAH). Sacubitril/valsartan, the angiotensin receptor II blocker-neprilysin inhibitor (ARNI), was recommended as the first-line therapy for patients with heart failure with reduced ejection fraction (HFrEF) by the 2021 European Society of Cardiology Guidelines. Although ARNI is effective in treating left ventricular (LV) enlargement and lower ejection fraction, its efficacy in treating individuals with PH and HF remains underexplored. Considering its vasodilatory effect at the pre-capillary level and a natriuretic drainage role at the post-capillary level, ARNI is believed to have a broad range of potential applications in treating PH-LHD. This review discusses the fundamental pathophysiological connections between PH and HF, emphasizing the latest research and potential benefits of ARNI in PH with various types of LHF and RV dysfunction.

A Rare Case of Severe Isolated Right Heart Failure with Secundum Type Atrial Septal Defect and Mitral Regurgitation Without Pulmonary Hypertension.

Typically, right heart failure (RHF) may occur following left heart failure (LHF) in chronic volume overload states such as chronic severe mitral regurgitation (MR) through chronically elevated pulmonary pressures. In Lutembacher syndrome (LS), the direct shunting through a secundum type atrial septal defect (ASD) results in congestive heart failure in the setting of severe mitral stenosis (MS) with or without elevated pulmonary arterial or venous pressures. We report a rare case of severe isolated RHF and bi-atrial enlargement resulting from the direct shunting through a secundum type ASD in the presence of a severe eccentric primary MR. There are no significant cases documented like this after a thorough search using PubMed, Medline, and Google Scholar. A review of the literature suggests that LS is also caused by a combination of mitral regurgitation and a secundum-type atrial septal defect without mitral stenosis, though rarely. Because this is a primary MR, we feel it is a case of LS with MR, ruling out a combination of secondary MR and secundum-type atrial septal defect.

The prevalence and survival of pulmonary hypertension due to left heart failure: A retrospective analysis of a multicenter prospective cohort study.

Background: Pulmonary hypertension due to left heart failure (PH-LHF) is currently the most common form of pulmonary hypertension (PH) encountered in clinical practice. Despite significant advances that have improved our understanding of PH-LHF over the past two decades, the mortality is still high in recent decades. This study aimed to describe the prevalence and survival of patients with PH-LHF, and explored the potential risk factors which may predict the prognosis of PH-LHF. Methods: A retrospective analysis of a prospective cohort study of left heart failure (LHF) patients who underwent right heart catheterization (RHC) between January 2013 and November 2016 was performed. The endpoint was all-cause mortality. Follow-ups were performed every 6 months ± 2 weeks. Results: A total of 480 patients with LHF were enrolled, with 215 (44.8%) having PH-LHF. The proportion of PH-LHF was significantly lower in coronary artery disease (CAD) group than without CAD (41.3 vs. 57.8%, p = 0.003). However, multivariable logistic regression analysis revealed that CAD was not associated with PH-LHF (Adjusted OR: 1.055, 95% CI: 0.576 - 1.935, p = 0.862). 75 of 215 (34.9%) patients with PH-LHF died during a median follow-up period of 84.6 months. The 1-, 3-, 5-, and 8-year survival rates of all PH-LHF patients were 94.3, 76.9, 65.8, and 60.2%, respectively. New York Heart Association Functional Class (NYHA FC), hemoglobin, and systolic pulmonary artery pressure (sPAP) were associated with mortality of PH-LHF in multivariate Cox analysis. Conclusion: PH is commonly identified in patients with LHF, with a prevalence of approximately 45%. The mortality is still high in patients with PH-LHF. NYHA FC, hemoglobin, and sPAP are independent risk predictors of mortality for PH-LHF. These findings may be useful for risk stratification in future clinical trial enrollment.

Impact of borderline pulmonary hypertension due to left heart failure on mortality in a multicenter registry study: A 3-year survivorship analysis.

Background: Patients with left heart failure (LHF) are often associated with the development of pulmonary hypertension (PH) which leads to an increased risk of death. Recently, the diagnostic standard for PH has changed from mean pulmonary arterial pressure (mPAP) ≥25 mmHg to >20 mmHg. Nonetheless, the effect of borderline PH (mPAP: 21-24 mmHg) on the prognosis of LHF patients is unclear. This study aimed to investigate the relationship between borderline PH and 3-year clinical outcomes in LHF patients. Methods: A retrospective analysis of a prospective cohort study was done for LHF patients who underwent right heart catheterization (RHC) between January 2013 and November 2016. The primary outcome was all-cause mortality; the secondary outcome was rehospitalization. Results: Among 344 patients, 62.5% were identified with a proportion of PH (mPAP ≥ 25), 10.8% with borderline PH (21-24), and 26.7% with non-PH (≤20), respectively. Multivariable Cox analysis revealed that borderline PH patients had a higher adjusted mortality risk (HR = 3.822; 95% CI: 1.043-13.999; p = 0.043) than non-PH patients. When mPAP was treated as a continuous variable, the hazard ratio for death increased progressively with increasing mPAP starting at 20 mmHg (HR = 1.006; 95% CI: 1.001-1.012). There was no statistically significant difference in adjusted rehospitalization between borderline PH and non-PH patients (HR = 1.599; 95% CI: 0.833-3.067; p = 0.158). Conclusions: Borderline PH is independently related to increased 3-year mortality in LHF patients. Future research is needed to evaluate whether more close monitoring, and managing with an intensifier improves clinical outcomes in borderline PH caused by LHF. Clinical trials registration: www.clinicaltrials.gov NCT02164526.

Using Deep-Learning Algorithms to Simultaneously Identify Right and Left Ventricular Dysfunction From the Electrocardiogram.

OBJECTIVES: This study sought to develop DL models capable of comprehensively quantifying left and right ventricular dysfunction from ECG data in a large, diverse population. BACKGROUND: Rapid evaluation of left and right ventricular function using deep learning (DL) on electrocardiograms (ECGs) can assist diagnostic workflow. However, DL tools to estimate right ventricular (RV) function do not exist, whereas those to estimate left ventricular (LV) function are restricted to quantification of very low LV function only. METHODS: A multicenter study was conducted with data from 5 New York City hospitals: 4 for internal testing and 1 serving as external validation. We created novel DL models to classify left ventricular ejection fraction (LVEF) into categories derived from the latest universal definition of heart failure, estimate LVEF through regression, and predict a composite outcome of either RV systolic dysfunction or RV dilation. RESULTS: We obtained echocardiogram LVEF estimates for 147,636 patients paired to 715,890 ECGs. We used natural language processing (NLP) to extract RV size and systolic function information from 404,502 echocardiogram reports paired to 761,510 ECGs for 148,227 patients. For LVEF classification in internal testing, area under curve (AUC) at detection of LVEF ≤40%, 40% < LVEF ≤50%, and LVEF >50% was 0.94 (95% CI: 0.94-0.94), 0.82 (95% CI: 0.81-0.83), and 0.89 (95% CI: 0.89-0.89), respectively. For external validation, these results were 0.94 (95% CI: 0.94-0.95), 0.73 (95% CI: 0.72-0.74), and 0.87 (95% CI: 0.87-0.88). For regression, the mean absolute error was 5.84% (95% CI: 5.82%-5.85%) for internal testing and 6.14% (95% CI: 6.13%-6.16%) in external validation. For prediction of the composite RV outcome, AUC was 0.84 (95% CI: 0.84-0.84) in both internal testing and external validation. CONCLUSIONS: DL on ECG data can be used to create inexpensive screening, diagnostic, and predictive tools for both LV and RV dysfunction. Such tools may bridge the applicability of ECGs and echocardiography and enable prioritization of patients for further interventions for either sided failure progressing to biventricular disease.

PTEN as a Therapeutic Target in Pulmonary Hypertension Secondary to Left-heart Failure: Effect of HO-3867 and Supplemental Oxygenation.

Pulmonary hypertension (PH) is a condition when the pressure in the lung blood vessels is elevated. This leads to increase in thickness of the blood vessels and increases the workload of the heart and lungs. The incidence and prevalence of PH has been on the increase in the last decade. It is estimated that PH affects about 1% of the global population and about 10% of individuals >65 years of age. Of the various types, Group 2 PH is the most common type seen in the elderly population. Fixed PH or PH refractive to therapies is considered a contraindication for heart transplantation; the 30-day mortality in heart transplant recipients is significantly increased in the subset of this population. In general, the pathobiology of PH involves multiple factors including hypoxia, oxidative stress, growth factor receptors, vascular stress, etc. Hence, it is challenging and important to identify specific mechanisms, diagnosis and develop effective therapeutic strategies. The focus of this manuscript is to review some of the important pathobiological processes and mechanisms in the development of PH. Results from our previously reported studies, including targeted treatments along with some new data on PH secondary to left-heart failure, are presented.