Rahme, Serena

ABSTRACT Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is a serious complication which may necessitate temporary mechanical support in refractory cases. Here we describe a 63‐year‐old man with end‐stage ischemic cardiomyopathy and severe combined pre‐ and post‐capillary pulmonary hypertension who developed persistent RV failure post‐LVAD. He was intolerant to speed optimization secondary to preload mismatch, and invasive hemodynamics confirmed LV underfilling. An Impella RP Flex was placed for RV support, and biventricular (BiV) pressure‐volume (PV) loops were utilized to ascertain hemodynamic response. With increasing Impella RP Flex support, left ventricular end‐diastolic volume increased with subsequent improvement in left ventricular performance. This case represents the first reported use of BiV PV loop analysis to characterize the physiological effects of Impella RP Flex in a patient with LVAD support, underscoring its utility in understanding device‐ventricular interactions.

Background The Impella 5.5 is employed to provide left ventricular support in cardiogenic shock. Mechanistic understanding of biventricular relationships is essential in device optimization. Using a porcine model of acute myocardial infarction in tandem with pressure–volume loops, this study aimed to understand the impact of Impella 5.5 on biventricular hemodynamics. Methods Using Domestic Yorkshire pigs, an Impella 5.5 was inserted percutaneously under fluoroscopic guidance via carotid/aortic access and an acute myocardial infarction was created. Biventricular pressure–volume loops and derived parameters were generated for each level of support before (n=6) and after myocardial infarction (n=6). Results With increasing Impella 5.5 support, left ventricular pressure–volume loops shifted left, and right ventricular (RV) loops shifted right. In a healthy porcine heart, the RV adequately compensated for increased preload from the device, demonstrated by increased RV performance at higher P levels. After myocardial infarction, pigs were unable to tolerate speeds beyond P7 from diminished RV stroke volume reserve compared to healthy hearts. Median RV stroke volume percentage change from P1 to P9 before myocardial infarction was from 5.7% (interquartile range, −15.1% to 9.7%) to 50.6% (interquartile range, −11.6% to 60.2; P <0.05), and following acute myocardial infarction from P1 to P7 was from 3.9% (interquartile range, −2.7 to 78.4) to 13.4% (interquartile range, −8.9% to 147.2; P =0.94). Conclusions Impella 5.5 speed modulation highlights significant interventricular interactions with opposing biventricular trends. While the heart can mount an improvement in RV stroke volume with increasing Impella 5.5 support, these data suggest an attenuated response following acute myocardial infarction, which may relate to inadequate response to increased preload needed by the device after infarction affecting the interventricular septum.

Abstract Aims We aimed to assess regression and development rates of ≥moderate secondary mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with heart failure and reduced ejection fraction (HFrEF) receiving contemporary guideline-directed medical therapy (GDMT). Methods Patients with a &lt;1 year diagnosis of HFrEF with mildly (40% ≤ EF &lt; 50%) or moderately (&lt;40%) reduced EF enrolled in GDMT titration programme 2019–2024 were identified. Regression rates of ≥moderate MR/TR to ≤mild and development rates of incident ≥moderate MR/TR were calculated. Results Among 844 patients [median age 64; 68% men; 26% mildly reduced EF; 24% New York Heart Association (NYHA) Class III/IV], 28% had ≥moderate MR and 14% had ≥moderate TR. Over median 7.1 months, 171 (75%) patients with ≥moderate MR and 87 (75%) of patients with ≥moderate TR experienced regression to no/mild MR and TR, respectively. Conversely, over median 13 months, incident ≥moderate MR and TR developed in 5% and 6%, respectively, of patients with no/mild baseline MR and TR. Number of GDMT medications at follow-up was less in patients who did not have MR/TR regression (vs who did) and in patients who developed MR/TR (vs who did not). Patients with NYHA Class I/II received a similar number of GDMT and had a similar rate of MR and TR regression and development vs patients with NYHA Class III/IV. However, patients with mildly reduced EF received less GDMT medications vs patients with moderately reduced EF and experienced less MR regression. Conclusion In patients with a recent diagnosis of HFrEF receiving contemporary GDMT, the majority with ≥moderate secondary MR and TR achieved regression of MR/TR, and the minority without significant baseline MR/TR developed ≥moderate regurgitation at follow-up.

Introduction: The Impella 5.5 is frequently employed to provide temporary mechanical circulatory support as bridge to recovery or durable therapy. Optimization of device management relies on understanding ventricular pressure-volume (PV) relationships. Aim: The aim of this study was to evaluate the biventricular (BiV) relationship with PV loop assessment during Impella 5.5 support in non-myopathic ventricles. Methods: Six domestic Yorkshire Pigs were used for this study. The Impella 5.5 (J&J MedTech, NJ) was inserted percutaneously under ultrasound and fluoroscopic guidance through either the carotid artery or aortic arch, using a 26Fr DrySeal Sheath (Gore, AZ). BiV PV loop conductance catheters (Sigma-M, CD Leycom, Hengelo, The Netherlands) were inserted via femoral venous access. The LV PV loop catheter is positioned via transeptal puncture and with intracardiac echocardiogram guidance. BiV PV loops are generated for each level of Impella 5.5 support. Results: With increasing levels of Impella 5.5 support, left ventricular (LV) PV loops shifted increasingly to the left and right ventricular (RV) loops to the right. Accordingly, LV end-diastolic volume (EDV) decreased (110±4 ml to 90±8 ml; p<0.001) and RV EDV increased (121±7 ml to 147±13 ml; p<0.001), from baseline to P9. Native LV systolic function decreased with increasing Impella 5.5 support, as demonstrated by a reduction in stroke volume (SV) (56±5 ml to 49±5 ml; p<0.001), cardiac output (CO) (3.4±0.8 ml/min to 2.0±0.3 ml/min; p<0.001), ejection fraction (EF) (51±4% to 44±6%; p<0.001), stroke work (SW) (4483±1023 ml*mmHg to 2383±719 ml*mmHg; p<0.001), and LV peak positive dP/dt (825 ± 184 mmHg/s to 523 ± 99 mmHg/s; p<0.001). Conversely, the native RV experienced preload-mediated increase in SV (65±7 ml to 86±20 ml; p<0.001), CO (3.7±0.8 ml/min to 4.3±0.9 ml/min; p<0.001), EF (53±4% to 58±11%; p<0.001), SW (918±143 ml*mmHg to 1529±365 ml*mmHg; p<0.001), and RV dP/dt (164±16 mmHg/s to 228±29 mmHg/s, p<0.001). Load independent contractility was assessed in the LV (1.64±0.33 mmHg/ml to 1.71±0.41 mmHg/ml; p=0.2) and RV (0.25±0.04 mmHg/ml to 0.29±0.05 mmHg/ml; p<0.001). Conclusions: This study highlights ventricular interdependence with Impella 5.5 support with opposing BiV trends. In a healthy heart, the RV can adequately compensate for increased preload offered by the device.

Introduction: Microaxial flow pumps reduce mortality in myocardial infarction (MI) related cardiogenic shock (CS). The Impella 5.5 generates increased flow to provide circulatory support, and optimization relies on mechanistic understanding of pressure-volume (PV) relationships. Aim: Using a porcine model of acute MI in tandem with biventricular (BiV) PV loop conductance catheters, this study aimed to understand the impact of Impella 5.5 on BiV hemodynamics in MI CS. Methods: In 6 Domestic Yorkshire Pigs, an Impella 5.5 (J&J MedTech, NJ) was inserted percutaneously under fluoroscopic guidance via carotid or aortic access. An angioplasty balloon catheter was advanced past the first diagonal and inflated to above nominal pressure with blood flow obstruction for 90 minutes. BiV PV loop conductance catheters (Sigma-M, CD Leycom, Hengelo, The Netherlands) were inserted via femoral venous access. The left ventricle (LV) PV loop catheter is positioned via transeptal puncture using intracardiac echocardiography. BiV PV loops are generated for each level of Impella support from P1 to P7. Results: With increasing Impella 5.5 support, LV PV loops shifted to the left and right ventricular (RV) loops to the right. Without statistical significance, LV end diastolic volume (EDV) decreased by a mean of 12.3 ± 10.7% from baseline and RV EDV increased by 32 ± 40%. Native LV function decreased with increasing Impella 5.5 support, demonstrated by a reduction in stroke volume (SV) (35±13 ml to 27±14 ml; p<0.001), cardiac output (CO) derived from SV&heart rate (2.0±0.5 ml/min to 1.7±0.7 ml/min; p<0.001), and ejection fraction (EF) (37±7% to 29±12%; p<0.001). Less consistent trends were noted in peak positive dP/dt and end-systolic pressure volume relationship. Native RV function increased with higher levels of Impella 5.5 support, noted by increasing SV (27±24 ml to 41±28 ml; p=0.004), CO (1.6±1.2 ml/min to 2.3±1.4 ml/min; p=0.001), and EF (42±16% to 45±9%; p=0.04). Arterial elastance and ventriculo-arterial coupling increased in the LV from baseline to P7 (2.2±1.4 mmHg/ml to 2.8±1.0 mmHg/ml and 1.8±0.5 to 3.2±1.9, respectively; p<0.001) and decreased in the RV (1.3±0.7 mmHg/ml to 0.9±0.7 mmHg/ml (p<0.001) and 2.1±2.2 to 1.3±0.6 (p=0.004)). Conclusions: Impella 5.5 speed modulation highlights significant ventricular interdependence in the setting of acute MI. PV loop derived parameters here visualized parameters that may be utilized to improve optimization of hemodynamic support in CS.

Background Mitral valve prolapse (MVP) can be associated with ventricular arrhythmias (VA), but little is known about the relationship between VA and exercise in these patients. The aim of this study was to assess the occurrence and severity of VA during exercise tests in patients with MVP, and to explore the association between VA during exercise and the occurrence of arrhythmic events during follow-up. Methods In this multicentre study, 375 patients with MVP (58 (48–69) years, 53% male) who underwent a clinically indicated exercise test were included. Severity of VA during exercise was defined as: (1) no VA, (2) minor VA (premature ventricular contractions ≥5% or non-sustained ventricular tachycardia (nsVT) <120 beats per minute) and (3) major VA (nsVTs ≥120 beats per minute). Results During exercise test, 242 (65%) patients showed no VA, 88 (24%) minor VA and 45 (12%) major VA. Patients with minor and major VAs showed more often bileaflet prolapse and mitral annular disjunction (MAD) than patients with no VA (p<0.001). Over a median follow-up of 101 months (IQR 58–138 months), 35 patients (9%) developed a severe arrhythmic event, defined as sustained VA or ventricular fibrillation, implantation of an implantable cardioverter-defibrillator and VA ablation. At the Kaplan-Meier curve analysis, patients with major VA showed the worst arrhythmic event-free survival (log-rank p<0.001). On multivariable analysis, left ventricular end-systolic diameter, MAD and VA severity during exercise were independently associated with this outcome. Conclusions In patients with MVP, the occurrence of VA during exercise is associated with more advanced mitral valve abnormalities, including MAD, and with higher rates of severe arrhythmic events during follow-up. Performing an exercise test, combined with the clinical and echocardiographic assessments, may therefore offer important complementary information useful for patient management.

Introduction: Anthracyclines (AC), a class of chemotherapeutic drugs, are used to treat various cancers, including breast cancer (BC). However, AC cause dose-dependent cardiac toxicity. Practice guidelines list pre-existing cardiomyopathy as a risk factor for cancer therapy-related cardiac dysfunction (CTRCD), but there is a lack of data on cardiotoxicity risk in patients with left ventricular (LV) hypertrabeculation without LV hypertrophy/dilation. We present a patient with LV hypertrabeculation who developed LV dysfunction after AC chemotherapy for BC. Description of Case: A 55-year-old woman diagnosed with multicentric invasive ductal carcinoma (IDC) of the right breast, stage IIA (cT3 cN1 cM0), grade 2, ER+/PR+/HER2-, was treated with neoadjuvant Paclitaxel for 3 months. Before AC-based chemotherapy, stress cardiac MRI due to residual post-COVID-19 dyspnea showed LV hypertrabeculation with a non-compacted/compacted ratio of 2.3, LVEF 56%, and no delayed enhancement. Transthoracic echocardiography (TTE) reported an LVEF of 52% with GLS of -17%. The patient's electrocardiogram (ECG) showed normal sinus rhythm, and NT-pro BNP levels were <20 pg/mL. Genetic testing identified a rare variant in MYH7-encoded myosin heavy chain 7 (p.Arg941Leu-MYH7). She had no cardiovascular (CV) risk factors or family history of CV disease. She then underwent 4 cycles of Doxorubicin (cumulative dose 232.2 mg/m2) and Cyclophosphamide, followed by bilateral mastectomy and adjuvant radiotherapy (5000 cGy in 25 fractions). One year after chemotherapy, follow-up TTE showed LVEF decreased to 45% with GLS of -17%. The patient’s ECG remained normal, and NT-pro BNP levels were <36 pg/mL. Despite an LVEF decline, not all criteria for CTRCD were met, suggesting a gene-environment interplay between her chemotherapy and pre-existing MYH7-mediated non-dilated LV cardiomyopathy (NDLVC) with hypertrabeculation. The patient has remained without symptoms of heart failure and is currently taking Letrozole 2.5 mg daily. Discussion: This case offers a unique perspective on a BC patient treated with AC chemotherapy, who has a possible MYH7-mediated NDLVC with hypertrabeculation, and who experienced an LVEF decline of indeterminate significance. While the association of her possible NDLVC with hypertrabeculation is uncertain, the safety of AC in patients with isolated hypertrabeculation or NDLVC with hypertrabeculation, as introduced by the 2023 ESC cardiomyopathy guidelines, remains to be defined.

Abstract Background Thromboembolic stroke risk remains a clinical challenge in cardiac amyloidosis (CA) patients with atrial fibrillation because of the increased prevalence of left atrial appendage thrombi irrespective of CHA2DS2-VASc score and a higher prevalence of factors that increase the risk of bleeding with anticoagulation. Left atrial appendage closure (LAAC) is an effective option in patients with atrial fibrillation and high bleeding risk; however, data describing a LAAC strategy for stroke prevention in patients with CA is limited. Among non-CA patients, procedural success and serious complication rates are around 98% and 3% respectively. Purpose In this multicenter retrospective study, we aimed to investigate whether left atrial appendage closure (LAAC) could reduce the risk of bleeding complications and ischemic cerebrovascular events in patients with CA. Methods In an international multi-center retrospective study, patients with CA that underwent LAAC were included. The diagnosis of CA was established on the basis of histologic confirmation or advanced multimodality cardiac imaging as per current consensus statements. Results A total of 28 patients (93% male; 87% ATTR-CA; 13% AL-CA; mean age 80 years) met inclusion criteria. At baseline, mean CHA2DS2-VASc and HAS-BLED scores were 4 and 3 respectively, mean left ventricular ejection fraction was 50%, and mean indexed left atrial volume was 58 mL/m2. 21% of patients had a prior history of ischemic stroke, 14% prior history of hemorrhagic stroke, 7% prior transient ischemic attack, and 54% had a prior history of major or minor bleeding. Procedural success was achieved in 26 patients (93%) with procedural complications occurring in 2 patients (vascular access site bleeding and cardiac tamponade). Regarding in-hospital and follow-up complications, 0% ischemic stroke, 0% hemorrhagic stroke, and major or minor bleeding in 4% of patients. During follow up, device thrombosis occurred in only 1 patient. Conclusion LAAC is a feasible and effective alternative to anticoagulation in patients with CA and excessive bleeding risk, with procedural success and complication rates similar to reported studies of non-CA patients.

Background Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce. Methods In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT). Results Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58–74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7–3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4–3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS. Conclusions Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.