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AIMS: Patients with type 2 diabetes (T2D) have a high prevalence of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF), which in turn leads to an increased risk of hospitalization and death. However, the factors of risk and their relative importance in leading to higher left ventricular filling pressures are still disputed. We sought to clarify the associations of a wide range of invasive and non-invasive risk factors with cardiac filling pressures in high-risk T2D patients. METHODS AND RESULTS: Patients with T2D at high risk of cardiovascular events were prospectively enrolled in this study. Participants were thoroughly phenotyped including right heart catheterization at rest and during exercise, echocardiography, urinary excretion of albumin (UACR), and quantification of their myocardial blood flow rate (MFR) using cardiac 82Rb-PET/CT. Of the 37 patients included in the study, 22 (59%) patients met invasive criteria for HFpEF. Only 2 out of 39 variables emerged as independent factors associated with left ventricular filling pressure as assessed by pulmonary capillary wedge pressure (PCWP) at rest; history of hypertension (coefficient: 2.6 mmHg [0.3; 5.0], P = 0.030) and MFR (P = 0.026). We found a significant inverse association between MFR and PCWP with a coefficient of -2.3 mmHg (-4.3; -0.3) in PCWP per integer change of MFR. The MFR ranged from 1.18 to 3.68 in our study, which corresponds to a difference in PCWP of approximately 6 mmHg between patients with the lowest compared to the highest MFR. During exercise, only 2 variables emerged as borderline independent factors associated with PCWP: myocardial flow reserve (coefficient: -4.4 [-9.6; 0.8], P = 0.091) and beta-blockers use (coefficient: 6.1 [-0.1; 12.4], P = 0.053). CONCLUSIONS: In patients with type 2 diabetes without known HFpEF but risk factors for cardiovascular disease, myocardial blood flow rate was independently associated with PCWP at rest across the range from normal to abnormal left heart filling pressures. A clinically significant difference of 6 mmHg in PWCP was attributable to differences in MFR in patients with the lowest compared with the highest MFR values. This suggests that strategies than attenuate microvascular dysfunction could slow progression of increased left ventricular left heart filling pressures in patients at increased risk.

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Background: Pulmonary capillary wedge pressure (PCWP) is often used as a surrogate for left-ventricular end-diastolic pressure in patients (LVEDP) who are on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support for cardiogenic shock and cardiac arrest. However, the correlation between PCWP and LVEDP is not clear in the setting of V-A ECMO usage. We sought to evaluate this correlation in this case series. Methods: Patients were referred to our cardiac catheterization laboratory for invasive hemodynamic studies to assess their readiness for VA-ECMO decannulation. All patients underwent simultaneous left and right heart catheterization. Using standard techniques, we measured PCWP and LVEDP simultaneously. Continuous variables were reported as medians with interquartile ranges. The correlation between PCWP and LVEDP was evaluated using simple linear regression and reported as R2. Results: Four patients underwent invasive hemodynamic studies 4 (2.5, 7) days after VA-ECMO cannulation. All four patients had suffered in-hospital cardiac arrest and had been put on VA-ECMO. At the baseline level of VA-ECMO flow of 4.1 (3.8, 4.4) L/min, the median LVEDP and PCWP were 6 (4, 7.5) mmHg and 12 (6.5, 16) mmHg, respectively. At the lowest level of VA-ECMO flow of 1.9 (1.6, 2.0) L/min, the median LVEDP and PCWP was 13.5 (8.5, 16) mmHg and 15 (13, 18) mmHg, respectively. There was a poor correlation between the simultaneously measured PCWP and LVEDP (R2 = 0.03, p = 0.66). Conclusions: The PCWP may not correlate well with LVEDP in patients treated with VA-ECMO, particularly at high levels of VA-ECMO support.

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Background: Maintaining a low left atrial pressure (LAP) in off-pump coronary artery bypass grafting (OPCAB) is desirable. This study was done to compare the effects of intravenous levosimendan or milrinone on LAP at different stages of OPCAB. Materials and Methods: After institutional ethics committee clearance, this two-arm double-blind randomized control trial was done in 44 adult patients with triple vessel coronary artery disease undergoing OPCAB at cardiac OT of IPGME&R, Kolkata. The patients were randomly allocated into two groups receiving intraoperative either levosimendan or milrinone. Pulmonary capillary wedge pressure (PCWP) was compared as the primary outcome parameter, whereas other echocardiographic and hemodynamic parameters were also assessed during six stages of OPCAB, that is, after sternotomy, proximal(s), left anterior descending artery (LAD), obtuse marginal (OM), posterior descending artery (PDA) grafting, and before sternal closure. Numerical parameters were compared using Student's unpaired two-tailed t-test. Results: PCWP was found to be significantly lower (P < 0.05) in the levosimendan group during proximal (P = 0.047), LAD (P = 0.018), OM (P < 0.0001), PDA grafting (P = 0.028), and before sternal closure (P = 0.015). Other parameters indicate LAP, that is, from mitral early diastolic inflow velocity to mitral annular early diastolic velocity ratio (E/e'), which indicated significantly lower LAP in levosimendan group during LAD, OM, and PDA grafting and before sternal closure. Conclusion: Levosimendan may be used as a primary inotrope in terms of better reduction in left atrial pressure during different stages of OPCAB, translating to a decrease in left ventricular end-diastolic pressure, therefore maintaining optimum coronary perfusion pressure, which is the primary goal of the surgery.

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Background: Percutaneous mitral valve repair (PMVR) has evolved to be a standard procedure in suitable patients with mitral regurgitation (MR) not accessible for open surgery. Here, we analyzed the influence of the number and positioning of the clips implanted during the procedure on MR reduction analyzing also sub-collectives of functional and degenerative MR (DMR). Results: We included 410 patients with severe MR undergoing PMVR using the MitraClip® System. MR and reduction of MR were analyzed by TEE at the beginning and at the end of the PMVR procedure. To specify the clip localization, we sub-divided segment 2 into 3 sub-segments using the segmental classification of the mitral valve. Results: We found an enhanced reduction of MR predominantly in DMR patients who received more than one clip. Implantation of only one clip led to a higher MR reduction in patients with functional MR (FMR) in comparison to patients with DMR. No significant differences concerning pressure gradients could be observed in degenerative MR patients regardless of the number of clips implanted. A deterioration of half a grade of the achieved MR reduction was observed 6 months post-PMVR independent of the number of implanted clips with a better stability in FMR patients, who got 3 clips compared to patients with only one clip. Conclusions: In patients with FMR, after 6 months the reduction of MR was more stable with an increased number of implanted clips, which suggests that this specific patient collective may benefit from a higher number of clips.

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Introduction: A cornerstone of heart failure assessment is the right heart catheterization and the pulmonary capillary wedge pressure measurement it can provide. Clinical and hemodynamic parameters such as weight and jugular venous distention are less invasive measures often used to diagnose, manage, and treat these patients. To date, there is little data looking at the association of these key parameters to measured pulmonary capillary wedge pressure (PCWP). This is a large, retrospective, secondary analysis of a right heart catheterization database comparing clinical and hemodynamic parameters against measured PCWP in heart failure patients. Methods: A total of 538 subjects were included in this secondary analysis. Spearman's Rho analysis of each clinical and hemodynamic variable was used to compare their association to the documented PCWP. Variables analyzed included weight, body mass index (BMI), jugular venous distention (JVD), creatinine, edema grade, right atrial pressure (RAP), pulmonary artery systolic pressure (PASP), systemic vascular resistance, pulmonary vascular resistance, cardiac output (thermal and Fick), systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, oxygen saturation (SpO2), and pulmonary artery diastolic pressure (PADP). Results: Ten out of 17 selected parameters had a statistically significant association with measured PCWP values. PADP had the strongest association (0.73, p<0.0001), followed by RAP and PASP (0.69, p<0.0001 and 0.67, p<0.0001, respectively). Other significant parameters included weight (0.2, p<0.001), BMI (0.2, p<0.001), SpO2 (-0.17, p<0.0091), JVD (0.24, p<0.005) and edema grade (0.2, p<0.0001). Conclusion: This retrospective analysis clarifies the associations of commonly used clinical and hemodynamic parameters to the clinically used gold standard for volume assessment in heart failure patients, PCWP.

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An 80-year-old man with severe nonischemic cardiomyopathy status post left ventricular assist device (LVAD) placement 11 years prior presented for recurrent LVAD alarms from internal driveline fracture. Given his partial myocardial recovery and his preference to avoid surgical procedures, percutaneous LVAD decommissioning was performed by occlusion of the outflow graft and subsequently driveline removal. (Level of Difficulty: Advanced.).

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We describe a case of severe biventricular failure and cardiovascular collapse following exposure to the manure gas hydrogen sulfide. Initial tests indicated uncoupling of cellular bioenergetics in addition to myocardial damage. Cardiopulmonary support with venoarterial extracorporeal membrane oxygenation was initiated, and the patient could be successfully weaned from support after 28 days. (Level of Difficulty: Advanced.).

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A 37-year-old man was referred for consideration of percutaneous decommissioning of a left ventricular assist device (LVAD). Following careful hemodynamic monitoring during pump turn-down and temporary outflow graft occlusion, the LVAD was permanently decommissioned by using a vascular plug to induce thrombosis of the outflow graft. (Level of Difficulty: Advanced.).

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Background: Right ventricular (RV) afterload is widely assessed by pulmonary vascular resistance (PVR). However, RV afterload is underestimated because PVR does not account for the pulsatile load. The pulsatile load is often evaluated by pulmonary arterial compliance (PAC). The RC (resistance-compliance) time, which is calculated from the product of PVR and PAC, is considered to remain constant under medical therapy. However, little is known on how RC time is affected by invasive therapy in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to evaluate change of RC time in patients underwent pulmonary endarterectomy (PEA). Furthermore, we investigated the clinical relevance of RC time. Methods: We reviewed consecutive 50 patients except for death case underwent PEA. Baseline clinical parameters including RC time before performing PEA and follow-up were evaluated. Patients was classified as decrease or non-decrease according to change of RC time. Furthermore, we classified patients into a NYHA I group who had no symptom after treatment and a residual symptom group in order to investigate the relationship of RC time to residual symptoms. Results: RC time was significantly decreased after PEA (0.54 ± 0.16 to 0.45 ± 0.12 sec, p < 0.001). Residual symptom after PEA of Decrease group were significantly better than that of Non-decrease group in RC time (12 patients, 40% vs. 11 patients, 78.6%, p < 0.02). Furthermore, multivariate analysis revealed that only RC time after PEA was independently associated with residual symptom (OR 1.026, 95% CI 1.005-1.048; p = 0.017). Conclusions: RC time was decreased after PEA, and might be a possible indicator for predicting PEA success.

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Introduction: Clinical symptoms of heart failure commonly include fatigue, edema, and shortness of breath. Unfortunately, clinical monitoring has proven unreliable in predicting congestion and the need for hospitalization. Biosensing wearables have been developed as a potential adjunct to clinical signs and symptoms to detect congestion before it becomes severe thus preventing a heart failure hospitalization. Hypothesis: Clinical signs and symptoms of heart failure will correlate with thoracic bioimpedance measurements (ZOE®) and pulmonary capillary wedge pressure (PCWP). Methods: One hundred and fifty-five subjects undergoing right heart catheterization (RHC) were prospectively enrolled. A Zo value (ohms) was obtained, jugular venous pressure (JVP) was estimated, edema graded, and shortness of breath (SOB) assessed in all subjects. RHC was performed by a scheduled cardiologist per routine. One-way ANOVA was performed to assess the relationship between variables. A Pearson correlation coefficient was used to compare the Zo value and PCWP. Results: Neither estimated JVP (cmH2O) (p = 0.65, n = 110) nor edema scores (p = 0.12, n = 110) demonstrated a significant relationship to PCWP. The presence of subjective SOB also did not demonstrate a significant association with PCWP (p = 0.99, n = 110). There was no correlation between ZOE® and PCWP (r = -0.08, p = 0.56, n = 56). Conclusions: These findings support the idea that traditional measures for monitoring heart failure patients are limited.

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We have shown that systemic and cardiac sympathetic activation is present in heart failure with preserved ejection fraction (HFpEF) patients. Conversely, whereas systemic inflammatory activation was also detected in HFpEF, we did not detect local myocardial release of inflammatory cytokines. Activation of the sympathetic system correlated with both hemodynamic and demographic factors that characteristically cluster together in HFpEF. Together these data suggest that there may be a role for antiadrenergic therapies in certain HFpEF patients. The study does not implicate locally derived cytokines in the myocardial biology of HFpEF, although systemic sources may contribute to the global pathophysiology of HFpEF.

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Chronic heart failure is one of the most debilitating chronic conditions affecting millions of people and adding a significant financial burden to health care systems worldwide. Despite the significant therapeutic advances achieved over the last decade, morbidity and mortality remain high. Multiple catheter-based interventional therapies targeting different physiological and anatomical targets are already under different stages of clinical investigation. The present paper provides a technical overview of the most relevant catheter-based interventional therapies under clinical investigation.

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BACKGROUND: Cirrhotic cardiomyopathy refers to the structural and functional changes in the heart leading to either impaired systolic, diastolic, electrocardiographic, and neurohormonal changes associated with cirrhosis and portal hypertension. Cirrhotic cardiomyopathy is present in 50% of patients with cirrhosis and is clinically seen as impaired contractility, diastolic dysfunction, hyperdynamic circulation, and electromechanical desynchrony such as QT prolongation. In this review, we will discuss the cardiac physiology principles underlying cirrhotic cardiomyopathy, imaging techniques such as cardiac magnetic resonance imaging and scintigraphy, cardiac biomarkers, and newer echocardiographic techniques such as tissue Doppler imaging and speckle tracking, and emerging treatments to improve outcomes. METHODS: We reviewed available literature from MEDLINE for randomized controlled trials, cohort studies, cross-sectional studies, and real-world outcomes using the search terms "cirrhotic cardiomyopathy," "left ventricular diastolic dysfunction," "heart failure in cirrhosis," "liver transplantation," and "coronary artery disease". RESULTS: Cirrhotic cardiomyopathy is associated with increased risk of complications such as hepatorenal syndrome, refractory ascites, impaired response to stressors including sepsis, bleeding or transplantation, poor health-related quality of life and increased morbidity and mortality. The evaluation of cirrhotic cardiomyopathy should also guide the feasibility of procedures such as transjugular intrahepatic portosystemic shunt, dose titration protocol of betablockers, and liver transplantation. The use of targeted heart rate reduction is of interest to improve cardiac filling and improve the cardiac output using repurposed heart failure drugs such as ivabradine. Liver transplantation may also reverse the cirrhotic cardiomyopathy; however, careful cardiac evaluation is necessary to rule out coronary artery disease and improve cardiac outcomes in the perioperative period. CONCLUSION: More data are needed on the new diagnostic criteria, molecular and biochemical changes, and repurposed drugs in cirrhotic cardiomyopathy. The use of advanced imaging techniques should be incorporated in clinical practice.

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Objectives: We compared posttransplant outcomes between patients bridged from temporary mechanical circulatory support to durable left ventricular assist device before transplant (bridge-to-bridge [BTB] strategy) and patients bridged from temporary mechanical circulatory support directly to transplant (bridge-to-transplant [BTT] strategy). Methods: We identified adult heart transplant recipients in the Organ Procurement and Transplantation Network database between 2005 and 2020 who were supported with extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary ventricular assist device as a BTB or BTT strategy. Kaplan-Meier survival analysis and Cox regressions were used to assess 1-year, 5-year, and 10-year survival. Posttransplant length of stay and complications were compared as secondary outcomes. Results: In total, 201 extracorporeal membrane oxygenation (61 BTB, 140 BTT), 1385 intra-aortic balloon pump (460 BTB, 925 BTT), and 234 temporary ventricular assist device (75 BTB, 159 BTT) patients were identified. For patients supported with extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary ventricular assist device, there were no differences in survival between BTB and BTT at 1 and 5 years posttransplant, as well as 10 years posttransplant even after adjusting for baseline characteristics. The extracorporeal membrane oxygenation BTB group had greater rates of acute rejection (32.8% vs 13.6%; P = .002) and lower rates of dialysis (1.6% vs 21.4%; P < .001). For intra-aortic balloon pump and temporary ventricular assist device patients, there were no differences in posttransplant length of stay, acute rejection, airway compromise, stroke, dialysis, or pacemaker insertion between BTB and BTT recipients. Conclusions: BTB patients have similar short- and midterm posttransplant survival as BTT patients. Future studies should continue to investigate the tradeoff between prolonged temporary mechanical circulatory support versus transitioning to durable mechanical circulatory support.

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BACKGROUND: Heart failure is the leading cause of hospitalization in the elderly and readmission is common. Clinical indicators of congestion may not precede acute congestion with enough time to prevent hospital admission for heart failure. Thus, there is a large and unmet need for accurate, noninvasive assessment of congestion. Noninvasive venous waveform analysis in heart failure (NIVAHF) is a novel, noninvasive technology that monitors intravascular volume status and hemodynamic congestion. The objective of this study was to determine the correlation of NIVAHF with pulmonary capillary wedge pressure (PCWP) and the ability of NIVAHF to predict 30-day admission after right heart catheterization. METHODS AND RESULTS: The prototype NIVAHF device was compared with the PCWP in 106 patients undergoing right heart catheterization. The NIVAHF algorithm was developed and trained to estimate the PCWP. NIVA scores and central hemodynamic parameters (PCWP, pulmonary artery diastolic pressure, and cardiac output) were evaluated in 84 patients undergoing outpatient right heart catheterization. Receiver operating characteristic curves were used to determine whether a NIVA score predicted 30-day hospital admission. The NIVA score demonstrated a positive correlation with PCWP (r = 0.92, n = 106, P < .0001). The NIVA score at the time of hospital discharge predicted 30-day admission with an AUC of 0.84, a NIVA score of more than 18 predicted admission with a sensitivity of 91% and specificity of 56%. Residual analysis suggested that no single patient demographic confounded the predictive accuracy of the NIVA score. CONCLUSIONS: The NIVAHF score is a noninvasive monitoring technology that is designed to provide an estimate of PCWP. A NIVA score of more than 18 indicated an increased risk for 30-day hospital admission. This noninvasive measurement has the potential for guiding decongestive therapy and the prevention of hospital admission in patients with heart failure.

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An 80-year-old man with a destination left ventricular assist device (LVAD) presented with decompensated heart failure. Evaluation demonstrated numerous LVAD high power spike events, significant aortic regurgitation, and hemolysis. He underwent successful aortic valve replacement with a novel transcatheter valve and LVAD pump exchange that resulted in an improvement in his clinical status. (Level of Difficulty: Advanced.).

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Characterized by a rapidly increasing prevalence, elevated mortality and rehospitalization rates, and inadequacy of pharmaceutical therapies, heart failure with preserved ejection fraction (HFpEF) has motivated the widespread development of device-based solutions. HFpEF is a multifactorial disease of various etiologies and phenotypes, distinguished by diminished ventricular compliance, diastolic dysfunction, and symptoms of heart failure despite a normal ejection performance; these symptoms include pulmonary hypertension, limited cardiac reserve, autonomic imbalance, and exercise intolerance. Several types of atrial shunts, left ventricular expanders, stimulation-based therapies, and mechanical circulatory support devices are currently under development aiming to target one or more of these symptoms by addressing the associated mechanical or hemodynamic hallmarks. Although the majority of these solutions have shown promising results in clinical or preclinical studies, no device-based therapy has yet been approved for the treatment of patients with HFpEF. The purpose of this review is to discuss the rationale behind each of these devices and the findings from the initial testing phases, as well as the limitations and challenges associated with their clinical translation.

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Exercise hemodynamic catheterization is helpful to evaluate exertional symptoms when noninvasive investigations fail to provide an explanation in non-ischemic cardiomyopathy. In this case, a rate-related left bundle branch block resulted in severe dynamic mitral regurgitation and acute increase in pulmonary capillary wedge pressure. Cardiac resynchronization therapy resolved her symptoms. (Level of Difficulty: Intermediate.).

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Exercise intolerance remains one of the major factors determining quality of life in heart failure patients. In 6 patients with heart failure with preserved ejection fraction (HFpEF) undergoing invasive cardiopulmonary exercise testing, balloon inflation within the inferior vena cava (IVC) was performed during exercise to reduce and maintain pulmonary arterial (PA) pressures. Partial IVC occlusion significantly reduced PA pressures without reducing cardiac output. Partial IVC occlusion significantly reduced respiratory rate at matched levels of exercise. These findings highlight the importance of pulmonary pressures in the pathophysiology of HFpEF and suggest that therapies targeting hemodynamics may improve symptoms and exercise capacity in these patients.

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A lack of preclinical large animal models of heart failure with preserved ejection fraction (HFpEF) that recapitulate this comorbid-laden syndrome has led to the inability to tease out mechanistic insights and to test novel therapeutic strategies. This study developed a large animal model that integrated multiple comorbid determinants of HFpEF in a miniswine breed that exhibited sensitivity to obesity, metabolic syndrome, and vascular disease with overt clinical signs of heart failure. The combination of a Western diet and 11-deoxycorticosterone acetate salt-induced hypertension in the Göttingen miniswine led to the development of a novel large animal model of HFpEF that exhibited multiorgan involvement and a full spectrum of comorbidities associated with human HFpEF.