Preexisting Left Ventricular Dysfunction Research Articles

Multielectrode catheter-based pulsed field ablation of persistent and long-standing persistent atrial fibrillation

Abstract Background Rhythm control of non-paroxysmal atrial fibrillation (AF) is significantly more challenging, as a result of arrhythmia perpetuation promoting atrial substrate changes and AF maintenance. Purpose We describe a tailored ablation strategy targeting multiple left atrial (LA) sites via the multielectrode FarawaveTM pulsed field ablation (PFA) catheter in patients with persistent AF sustained beyond 6 months (PerAF>6m) and long-standing persistent AF (LSPAF). Methods The ablation protocol included the following stages: pulmonary vein antral and posterior wall isolation plus anterior roof line ablation (Stage 1); electrogram-guided substrate ablation (Stage 2); atrial tachyarrhythmia (AT) regionalization and ablation (Stage 3). Results Seventy-two [age:68±10y, 61.1%males; AF history: 25 (18-45) months] patients with PerAF>6m (52.8%) and LSPAF (47.2%) underwent their first PFA via the FarapulseTM system. LA substrate ablation (Stage 1 and 2) led to AF termination in 95.8% of patients. AF termination occurred while ablating the mitral edge of the postero-lateral ridge (40.3%), the inferior left atrium above the proximal coronary sinus (27.4%), the interatrial septum (22.6%), the superior aspect of the postero-lateral ridge (6.5%), the base of the appendage (3.2%). AF organized into a left-sided atrial flutter (AFlu) in 46 (74.2%) patients. The FarawaveTM catheter was used to identify LA sites showing diastolic, low-voltage electrograms and entrainment from its splines was performed to confirm the pacing site was inside the AFlu circuit (Figure 1). Left AFlu termination was achieved in all cases via PFA delivery. Total procedural and LA dwell times were 112±25min and 59±22 min, respectively. Major complications occurred in 2 (2.8%) patients with pre-existing left ventricular systolic dysfunction (EF<35%) who required inotropic therapy due to acute heart failure. Hemodynamics normalized within 24h and both patients were discharged after 2 and 3 additional hospital days. Transient ST-segment elevation was documented in 4 patients after peri-mitral PFA; timely nitrate administration led to ECG normalization within 10 minutes. Single-procedure success rate was 81.8% after 13.3±1.9 months of follow-up; AF-free survival was 93.1% (Figure 2). A subgroup of 36 patients completed a follow-up transthoracic echocardiography study to assess left atrial mechanical contraction changes after ablation. Median A-wave velocity was 30 (IQR: 20-35) cm/s post-ablation and 50 (IQR: 41-70) cm/s after a mean of 7.3±1.8 months post-ablation. Conclusions In our cohort, PFA-based AF substrate ablation led to AF termination in 95.8% of cases. Very favorable clinical outcomes were observed at one year of follow-up.Entrainment from the PFA Catheter.Kaplan-Meier Analysis.

Left ventricular systolic function in patients with acute coronary syndrome-risk profile

Abstract Funding Acknowledgements None. Introductions and objectives Left ventricular (LV) systolic dysfunction is one of the most important determinants of long-term outcome in acute coronary syndrome (ACS). Aim To determine the impact of the patient’s risk profile on the LV systolic function. Methods A single-center cross-sectional cohort study that included 3093 patients with ACS without pre-existing LV dysfunction. The comparison was performed between patients who did or did not develop a reduction in LV systolic function during the index event (<50%/≥50%), analyzing patients’ demographic, clinical, biochemical data, LV functional data, and anatomical distribution of the coronary artery disease (CAD). Result 1369 patients out of 3093 developed LV systolic dysfunction (44.3%). They were predominantly males 75.1% (1028), p=0.002; older (63.39±11.04 vs 61.21±11.12, p<0.00000); had higher level of cardiac troponin (p=0.00002), higher stress glycemia (9.2±5.3; p=0.0000001), HbA1c (6.9±1.8, p=0.000003), WBC (11.7±4.1, p=0.00001), blood urea nitrogen (BUN) (6.8±3.7, p=0.000003), and creatinine (93.2±45.1 p=0.000167), and had anemia (OR 0.35 (CI 0.29–41, p=0.000012). They had more severe CAD (SINTAX score 16.8±8.4 p=0.000012). Patients with preserved LV systolic function were predominantly females (29.7%, OR 1.1 95% CI 1.0-1.2), p = 0.002), younger (p<0.00000), and severely metabolically burdened (hypothyreosis (2.7%, OR 1.28 95% CI 0.93-1.76, p=0.052), higher levels of triglycerides (2.2±1.7 vs 1.9±1.5, p = 0.001), cholesterol (5.3±1.4 vs 5.2±1.4, p = 0.002), non-HDL-C (4.1±1.5 vs 3.9±1.3, p=0.006), however less likely to have pre-existing DM (OR 0.8 (CI 0.78–0.92), p=0.000094). They were more often NSTEMI [851 (49.4%), p = 0.000012]. Independent variables associated with a reduction in LV function were: advanced age, male gender, previous DM and anemia, stress glycemia, WBC, creatinine, and BUN. Conclusion Patients who developed reduced LV function had a very specific risk profile with bigger neuro-hormonal activation and inflammation, higher degree of myocardial damage, and worse renal function, whereas those with preserved LV systolic function after ACS were younger, predominantly females, more severely metabolically burdened, more often with NSTEMI and without LAD involvement.

The role of pre-existing renal dysfunction on in-hospital morbidity and mortality in patients with acute coronary syndrome

Abstract Funding Acknowledgements None. Introduction The baseline renal function is an important predictor for the prognosis of patients with acute coronary syndrome (ACS). The aim of our study was to analyse the impact of pre-existing renal failure (RF) and the risk profile of patients with ACS on the development of in-hospital morbidity and mortality. Materials and methods This was a single-center cross-sectional cohort study on 2702 patients with ACS. The main exclusion criterion was pre-existing left ventricular (LV) dysfunction. Demographical and clinical characteristics, biochemical parameters, the anatomical distribution of coronary artery disease, and the final outcomes were analysed according to presence of RF at the moment of the index event. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease Study Group Equation (MDRD), where patients with eGFR<60 ml/min/1.73 m2 had moderate to severe renal dysfunction. Results 777 (22.3%) out of 2702 patients had eGFR <60 ml/min at the moment of the index event. These patients were predominantly female, 34.1% (333) vs.17.7% (444), p=0.0004,OR 1.921(95%CI 1.701-2.168);older (70.0±9.7vs.60.5±10.7;p <0.000). They had significantly higher values of cardiac troponin (p=0.007), stress glycemia (p=0.000019), glycated hemoglobin (p=0.000012), and WBC (p=0.00001), meaning the extent of myocardial injury was bigger, with a more activated neuro-hormonal and inflammatory response in the conditions of the notably widespread anatomical distribution of CAD. However, patients with significantly reduced eGFR were less likely to be offered coronary angiography and PCI treatment, OR 0.524 (95%CI 0.434–0.632),p <0.000. As expected, anemia predominated in these patients (RBC 4.88±0.75 vs 4.53±0.58, p=0.000001; OR 1.27 (95% CI 1.09-1.48), and Hgb 143.81±16.69 vs 132.03±21.34, p=0.00001). They had a significantly lower level of sodium (p=0.008) and a higher level of potassium (p=0.00003). Interestingly, patients with eGFR <60 ml/min had lower lipoprotein levels. In-hospital mortality rate was 4.2%, however, significantly higher in reduced eGFR group (12% vs 1.9%, OR 6.9 (95% CI 4.9–9.8), p <0.00004). These patients were more likely to develop acute kidney injury [25.7% vs. 1.3%, OR 1.6 (95% CI 1.3-1.9, p = 0.000021)], pulmonary oedema [8% vs. 1.8%, OR 1.12 (95% CI 1.02-1.23, p = 0.000021), and cardiogenic shock [19.5% vs. 2.6%, OR 1.22 (95% CI 1.2-1.4), p = 0.00023]. Independent variables associated with RF were: advanced age, female gender, extracardiac ASCVD, previous CVI, previous RAAS treatment, stress glycemia, triglyceride, cholesterol, LDL-C, Hgb, WBC, and potassium level. Conclusion Patients with reduced eGFR (<60 ml/min) have a very specific risk profile, as identified in our study, and reduced eGFR is a major contributor to the prognosis of ACS, highly responsible for in-hospital morbidity and mortality.Multivariate logistic regression analysis

Trastuzumab in patients with breast cancer and pre-existing left ventricular systolic dysfunction

BackgroundTrastuzumab is one of the most effective treatments in HER-2 positive breast cancer patients. However, it is associated with development of cardiomyopathy/heart failure (HF) which is often a limiting side effect and associated with overall adverse outcomes. As a result, patients with pre-existing LV systolic dysfunction (LVSD) are often excluded from receiving anti-HER-2 therapy, which may lead to less effective cancer treatment and worse prognosis.ObjectivesThe current study aims to evaluate the safety of trastuzumab in patients with HER-2 positive breast cancer and pre-existing LVSD.MethodsIn this retrospective cohort study, 36 consecutive patients at a single center in Iran with HER-2 positive breast cancer with asymptomatic mild LVSD with LVEF 40–53% without heart failure symptoms and those who were closely followed in the Cardio-Oncology clinic before initiating the treatment and then every two cycles of trastuzumab were included. As per the program standard protocol they received a beta-blocker (carvedilol) and ACE-I (Lisinopril), up to the maximum tolerated dose, if there were no contraindications. Patients underwent routine echocardiography with global longitudinal strain (GLS) assessment every 3 months per guideline recommendations and were followed up 6 months after the end of treatment. Primary composite outcomes included myocardial infarction (MI), cardiac arrhythmia, heart failure(HF) symptoms and cardiovascular death. Secondary outcome was ≥ 10% reduction in LVEF or ≥ 15% reduction in GLS compared to baseline. If the LVEF decreased below 40%, the treatment was temporarily interrupted for one or two cycles, and spironolactone was added to the patient’s treatment. If the LVEF improved ≥ 40%, trastuzumab was rechallenged. Data analysis was performed using IBM SPSS Statistics 24.0. Software. Patients’ characteristics were reported using descriptive statistics, and its association with drop in LVEF or GLS was assessed using Pearson chi-square or Mann-Whitney U test. A p-value of less than 0.05 was considered significant.ResultsThirty-six patients were included in the study. Primary composite outcome was noted in 1(2.8%) patient. LVEF reduction of ≥ 10% occurred in 6(16.7%) of the patients, and a GLS reduction of more than 15% was detected in 4 (11.1%) of the patients. There was a significant association between a ≥ 10% reduction in LVEF and baseline systolic blood pressure (P-value: 0.04). LVEF reduction below 40% was observed in 3 (8.3%) patients, where trastuzumab was interrupted. All of these three patients had obesity (Median BMI 34.11, IQR 9.12) and uncontrolled HTN, and one of them had symptoms of heart failure (NYHA class II), for whom the trastuzumab treatment was discontinued. Among two patients, after the temporary interruption of trastuzumab, and addition of spironolactone, LVEF improved to above 40%, and the treatment was restarted with close cardiac monitoring; therefore, they could complete the entire one-year treatment period.ConclusionsTreatment with trastuzumab seems to be safe in patients with pre-existing LVSD (LVEF = 40–53%). Such high-risk patients should be strictly monitored and cardiovascular risk factors, such as HTN should be regulated.

The Effect of Glycemic Control on Left Ventricular Function in Clinical and Experimental Diabetes

BackgroundGlycemic control in diabetes mellitus (DM) has not improved cardiovascular outcomes with normal left ventricular (LV) function. We assessed the effect on LV dysfunction using a canine model of LV dysfunction and DM, and in patients with DM and LV dysfunction. MethodsChronic LV dysfunction was produced by coronary microsphere embolization in 34 canines (15-25 kg). Following 8 weeks of stabilization, DM was induced in 24 canines and randomized to good or poor glycemic control for 3 months. Ten canines without DM were controls. Hemodynamic and Doppler echocardiographic data were obtained prior to and following pressure loading. We reviewed the Doppler-echocardiography at baseline and follow-up in 207 patients with DM with reduced ejection fraction (EF; median follow-up = 612 days) and 60 age- and sex-matched non-DM patients with normal EF. Laboratory results, medications, and incident adverse events from medical records were obtained. ResultsEF = 43.8% ± 11.2% for all canines at 8 weeks. Canines with poor glycemic control (hemoglobin [Hb]A1c = 8.05% ± 3.02%) demonstrated reduced LV mass and rate-corrected velocity of circumferential fiber shortening, compared to those with LV dysfunction (1.36 ± 0.73 vs 0.88 ± 0.13 circumference per second, P < 0.01). Good glycemic control (HbA1c = 3.88% ± 0.89%) demonstrated similar LV parameters, compared to controls (HbA1c = 2.99% ± 0.44%). EF was similar among groups. Patients with vs without DM were followed for up to 3 years. Patients with DM and poor glycemic control had reduced EF, lower rate-corrected velocity of circumferential fiber shortening = 0.93 ± 0.26 vs 1.11 ± 0.26, P < 0.001), and greater incidence of heart failure. ConclusionsPoor glycemic control had an adverse effect on preexisting LV dysfunction experimentally and in patients with type 2 diabetes.

Thirty-day and one-year outcomes following transcatheter mitral valve edge-to-edge repair versus transapical mitral valve replacement in patients with left ventricular dysfunction

A comparison of 30-day and 1-year clinical outcomes in patients with pre-existing left ventricular (LV) dysfunction undergoing transcatheter mitral valve edge-to-edge repair (TEER) or transcatheter transapical mitral valve replacement (TMVR) has not previously been reported. We aimed to compare 30-day and 1-year rates of all-cause and cardiovascular mortality as well as rehospitalisation for heart failure (HFH). All patients with severe (≥3+) symptomatic mitral regurgitation (MR) and an LV ejection fraction ≤50% who underwent TEER or TMVR over a 5-year period were evaluated. Ninety-six patients (50 TEER, age 80±9 years, 70% secondary MR and 46 TMVR, age 72±9 years, 91% secondary MR) were studied. Baseline demographic and transthoracic echocardiogram characteristics were well-matched, with the exception of age (TEER 80±9 vs TMVR 72±9; p=0.01). Successful device implantation occurred in 96% of TEER patients and 97.8% of TMVR patients. Ninety-two percent of TEER patients had ≤2+MR predischarge, whilst no TMVR patient had ≥1+MR (p<0.01). No significant difference in the combined endpoint of 30-day all-cause mortality or HFH was observed (p>0.05). At 1 year, freedom from all-cause mortality and HFH was 79.2% across the entire study population but was significantly higher in patients undergoing TEER (TEER: n=45 [90%] hazard ratio 11.26, 95% confidence interval [CI]: 10.59-11.93 vs TMVR: n=39 [67.4%] 95% CI: 10.09-11.33;p=0.008). Despite comparable rates of successful device implantation, MR reduction, and 30-day all-cause mortality/HFH, TEER patients had lower all-cause mortality and HFH rates at 1 year.

Adverse reactions to antiarrhythmic drugs

There are various types of adverse reactions to antiarrhythmic drugs (AADs). Proarrhythmia, which refers to an exacerbation of the preexisting arrhythmia or occurrence of a new arrhythmia, may occur under the therapeutic concentration of an AAD. Bradyarrhythmia is the most common type of proarrhythmia due to AADs, and prior myocardial infarction and old age are known risk factors. Atrial flutter with 1:1 atrioventricular conduction usually occurs during rhythm control of atrial fibrillation with class IC AADs. QT prolongation due to AADs, mainly class III AADs, elevates the risk of torsade de pointes by triggered activity due to early afterdepolarization. The addition of clinical factors that promote QT prolongation, such as hypokalemia, hypomagnesemia, female sex, and bradycardia, increases the risk of developing torsade de pointes. Proarrhythmic monomorphic ventricular tachycardia usually occurs as a result of slow conduction and disparity of refractoriness due to class IC AADs. In patients with preexisting left ventricular systolic dysfunction or structural heart disease, the risk of hypotension or cardiogenic shock caused by negative inotropic effects due to AADs should be considered. To prevent these major adverse reactions to AADs, we need to understand the electrophysiologic properties of AADs in detail. Furthermore, the risk of proarrhythmia could be heightened by interplay with clinical factors, such as electrolyte unbalances, heart rate, and hepatic/renal or myocardial dysfunction. Sufficient awareness about drug-drug interactions, which may affect the metabolism of AADs, will improve patient safety during the management of arrhythmia.

Genetic Predictors of Anthracycline Mediated Cardiomyopathy with Induction Chemotherapy in Acute Myeloid Leukemia (AML)

Introduction: Anthracycline induced cardiomyopathy (CMP) is a concern in AML patients (pts) induced with "7+3” (7 days of cytarabine and 3 days of an anthracycline) or liposomal cytarabine/daunorubicin (CPX-351, Vyxeos). However, it is not well understood (i) how common anthracycline CMP with the availability of routine echocardiography for baseline CMP screening and (ii) how often post induction CMP is the reason for not pursuing a potentially curative allogeneic stem cell transplant (allo-SCT). In addition, while it is known that the cumulative anthracycline dose and preexisting left ventricular dysfunction are risk factors for anthracycline mediated CMP, it is not known whether mutations recurrently mutated in myeloid neoplasms predict risk for anthracycline mediated CMP. Methods: AML pts treated at Dana-Farber Cancer Institute (2014-2022) with 7+3 or Vyxeos induction were included if they met the following criteria: (i) pre and post induction chemotherapy echocardiogram to assess the left ventricular ejection fraction (LVEF) and (ii) comprehensive next generation sequencing was obtained prior to treatment. Post induction CMP was defined as LVEF < 50%. We recorded cardiovascular comorbidities including hypertension (HTN), diabetes mellitus (DM), hyperlipidemia (HLD), coronary artery disease (CAD), severe valvular disease and smoking. Continuous variables were summarized as median (range, R), while categorical variables were reported as frequency (percentage). Univariable and multivariable regression analysis was performed to identify predictors of post induction CMP. Results: A total of 422 pts were included; 37 patients (8.8%) developed post induction CMP (Table 1). There were no statistical differences between age, AML subtype, prior cancer therapy and cumulative anthracycline dose (for prior cancer therapy and induction chemotherapy) between pts with and without post induction CMP. Only 3 pts in this cohort (0.7%) had an abnormal LVEF (<50%) pre induction arguing for a highly preselected pt population thought to be fit enough to receive anthracycline containing induction chemotherapy. The post induction LVEF was 43% (R 20-48%) and 60% (R 50-75%) for patients with and without post induction CMP (p<0.001); this corresponded to an absolute decrease in LVEF post induction compared to pre-induction of -18% and -3%, respectively (p<0.001). While 73% of pts without post induction CMP received an allo-SCT, only 46% of pts with post induction CMP received an allo-SCT (p<0.001). However, in only 4/20 pts with post induction CMP who did not receive an allo-SCT (20%) was the emergent CMP the sole reason for not pursuing an allo-SCT. In the other 16/20 pts, other medical reasons were the reason for not pursuing an allo-SCT including sepsis/fungal infection (7 pts), active disease (3 pts), allo-SCT not indicated given favorable genetics (2 pts) and other reasons (4 pts). In univariable and multivariable analysis, age, sex, cardiovascular risk factors and cumulative anthracycline dose did not predict an increased risk for anthracycline mediated CMP (Table 2). While myeloid mutations commonly seen in patients with clonal hematopoiesis (DNMT3A, TET2, ASXL1) did not predict an increased risk for CMP, presence of a JAK2 V617F mutation predicted a significantly increased risk of CMP in univariable (hazard rate [HR] 5.57, 95% CI: 1.14-22.1, p=0.019) and multivariable analysis (HR 5.91, 95% CI: 1.18-24.1, p=0.017). Interestingly, JAK2 V617F transgenic mice have been shown to develop cardiac hypertrophy and collagen fibrosis (Shi et al. Journal of Hematology & Oncology 2014) arguing for an underlying biological effect of JAK2 mutations on cardiac function. Conclusions: In a selected pt population with a normal pre-induction LVEF (99.3% of pts), 8% of pts developed post-induction CMP, however, in only 4/123 pts (3%) this was the sole reason for not receiving an allo-SCT. While cardiovascular risk factors and cumulative anthracycline dose were not predictive of post induction CMP, presence of a JAK2 V617V mutation (but not other myeloid mutations) was associated with an increased risk for anthracycline CMP. This association is intriguing as it could potentially help with patient selection at higher risk for anthracycline CMP (e.g. consideration of anthracycline free induction in JAK2 mutated pts). However, this will require validation in a larger patient cohort. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Atrial fibrillation-induced tachycardiomyopathy and heart failure: an underappreciated and elusive condition.

Many patients with persistent, chronic, or frequently recurring paroxysmal atrial fibrillation (AF) may develop a tachycardiomyopathy (TCM) with left ventricular (LV) dysfunction and heart failure (HF), which is reversible upon restoration and maintenance of sinus rhythm, when feasible, or via better and tighter ventricular rate (VR) control. Mechanisms involved in producing this leading cause of TCM (AF-TCM) include loss of atrial contraction, irregular heart rate, fast VR, neurohumoral activation, and structural myocardial changes. The most important of all mechanisms relates to optimal VR control, which seems to be an elusive target. Uncontrolled AF may also worsen preexisting LV dysfunction and exacerbate HF symptoms. Data, albeit less robust, also point to deleterious effects of slow VRs on LV function. Thus, a J-shaped relationship between VR and clinical outcome has been suggested, with the optimal VR control hovering at ~ 65bpm, ranging between 60 and 80bpm; VRs above and below this range may confer higher morbidity and mortality rates. A convergence of recent guidelines is noted towards a stricter rather than a more lenient VR control with target heart rate &lt; 80bpm at rest and &lt; 110bpm during moderate exercise which seems to prevent TCM or improve LV function and exercise capacity and relieve TCM-related symptoms and signs. Of course, restoring and maintaining sinus rhythm is always a most desirable target, when feasible, either with drugs or more likely with ablation. All these issues are herein reviewed, current guidelines are discussed and relevant data are tabulated and pictorially illustrated.

Living Donor Liver Transplantation in a Cohort of Recipients With Left Ventricular Systolic Dysfunction

Data on feasibility, management, and outcomes of liver transplantation (LT) in patients with pre-existing left ventricular systolic dysfunction (LVSD), severe coronary artery disease (CAD) or cirrhotic cardiomyopathy (CCM) is scarce. We reviewed outcomes of living donor liver transplantation (LDLT) in recipients with LVSD (ejection fraction [EF] < 50%) from our series of 1946 LDLT's performed between July 2010 and July 2018. LVSD was detected in 12 male patients with a mean age, BMI and MELD of 52 ± 9 years, 25 ± 5kg/m2, and 19±4 respectively. Out of these, 6 patients had CAD (2 with previous coronary artery bypass graft, 1 following recent percutaneous transluminal coronary angioplasty, 2 post myocardial infarction, 1 noncritical CAD), and 6 had CCM. The EF ranged from 25% to 45%. Ethanol was the predominant underlying etiology for cirrhosis (50%). During LDLT, 2 patients developed ventricular ectopic rhythm and were managed successfully with intravenous lidocaine. Stress cardiomyopathy manifested in 3 patients post operatively with decreased EF, of which 2 improved, while 1 needed IABP support and succumbed to multiorgan failure on 8th postoperative day (POD). Another patient died on POD30 due to septic shock. Both these patients had higher MELD scores (actual MELD), extremes of BMI (17.3and 35.8kg/m2) and were diabetic. There were no long-term cardiac deaths. The 1-year, and 5-year survival were 75%, and 66%, respectively. Among potential LT recipientswith LVSD, those with stable CAD and good performance status, and well optimized CCM patients may be considered for LDLT after careful risk stratification in experienced centers.

Transcatheter Mitral Valve Edge-to-Edge Repair Versus Transapical Mitral Valve Replacement in Patients With Left Ventricular Dysfunction

The efficacy of transcatheter mitral valve edge-to-edge repair (TEER) is well established. In selected patients, transapical transcatheter mitral valve replacement (TMVR) may be an alternative to TEER. A comparison of these techniques in patients with pre-existing left ventricular (LV) dysfunction has not previously been reported.

A Case of Multidisciplinary Approach to Post-Radiotherapy Dilative Cardiomyopathy Undergoing Elective Cesarean Delivery: Anesthetic and Intensive Care Management

Cardiovascular diseases are the most common non-obstetric cause of maternal death. These cases became more common thanks to the improvement in cardiovascular therapies. A multidisciplinary team is necessary to manage these pregnancies. A 32 years old women at the 25th week of gestation for acute heart failure in pre-existing left ventricular dysfunction induced by radio-chemotherapy admitted to the Coronary Unit of IRCCS Policlinico Universitario Agostino Gemelli for worsening of dyspneic symptoms and anuria not responding to diuretic therapy. At the echocardiogram: ejection fraction 30%, enlarged left atrium, systolic pulmonary arterial pressure 38 mmHg, bilateral pleural effusion, bilateral diffused pulmonary B lines. A multidisciplinary team composed by cardiologists, gynecologists, anesthesiologists, cardiac surgeons, neonatologists and bioethicists decided for an elective cesarean delivery at the 27th week of gestation in the hybrid cardio-thoracic operating theater. Anesthesia was provided by combined spinal-epidural technique under invasive continuous hemodynamic monitoring with the Edwards Lifesciences HemoSphere with Hypotension Prediction Index (HPI) and ForeSight technology (Edwards Lifesciences, Irvine, USA) through catheterization of the left radial artery. The femoral arteries were left available for extracorporeal circulation. Continuous norepinephrine infusion was started once liquor was collected in the spinal needle at a 0.1 mcg/kg/minute through a central line and was continued until the end of surgery. Fluid management consisted of a total of 200 ml of crystalloids. HPI values never reached alarm values (maximum value =10). The patient was discharged home on the 5th day after delivery with good hemodynamic compensation. The baby was intubated at birth and then gradually weaned from mechanical ventilation, then discharged.

Intra-Aortic Balloon Pumping in Acute Decompensated Heart Failure With Hypoperfusion: From Pathophysiology to Clinical Practice.

Trials on intra-aortic balloon pump (IABP) use in cardiogenic shock related to acute myocardial infarction have shown disappointing results. The role of IABP in cardiogenic shock treatment remains unclear, and new (potentially more potent) mechanical circulatory supports with arguably larger device profile are emerging. A reappraisal of the physiological premises of intra-aortic counterpulsation may underpin the rationale to maintain IABP as a valuable therapeutic option for patients with acute decompensated heart failure and tissue hypoperfusion. Several pathophysiological features differ between myocardial infarction- and acute decompensated heart failure-related hypoperfusion, encompassing cardiogenic shock severity, filling status, systemic vascular resistances rise, and adaptation to chronic (if preexisting) left ventricular dysfunction. IABP combines a more substantial effect on left ventricular afterload with a modest increase in cardiac output and would therefore be most suitable in clinical scenarios characterized by a disproportionate increase in afterload without profound hemodynamic compromise. The acute decompensated heart failure syndrome is characterized by exquisite afterload-sensitivity of cardiac output and may be an ideal setting for counterpulsation. Several hemodynamic variables have been shown to predict response to IABP within this scenario, potentially guiding appropriate patient selection. Finally, acute decompensated heart failure with hypoperfusion may frequently represent an end stage in the heart failure history: IABP may provide sufficient hemodynamic support and prompt end-organ function recovery in view of more definitive heart replacement therapies while preserving ambulation when used with a transaxillary approach.

Pulseless Electrical Activity as the Initial Cardiac Arrest Rhythm: Importance of Preexisting Left Ventricular Function.

BackgroundPulseless electrical activity (PEA) is a common initial rhythm in cardiac arrest. A substantial number of PEA arrests are caused by coronary ischemia in the setting of acute coronary occlusion, but the underlying mechanism is not well understood. We hypothesized that the initial rhythm in patients with acute coronary occlusion is more likely to be PEA than ventricular fibrillation in those with prearrest severe left ventricular dysfunction.Methods and ResultsWe studied the initial cardiac arrest rhythm induced by acute left anterior descending coronary occlusion in swine without and with preexisting severe left ventricular dysfunction induced by prior infarcts in non–left anterior descending coronary territories. Balloon occlusion resulted in ventricular fibrillation in 18 of 34 naïve animals, occurring 23.5±9.0 minutes following occlusion, and PEA in 1 animal. However, all 18 animals with severe prearrest left ventricular dysfunction (ejection fraction 15±5%) developed PEA 1.7±1.1 minutes after occlusion.ConclusionsAcute coronary ischemia in the setting of severe left ventricular dysfunction produces PEA because of acute pump failure, which occurs almost immediately after coronary occlusion. After the onset of coronary ischemia, PEA occurred significantly earlier than ventricular fibrillation (<2 minutes versus 20 minutes). These findings support the notion that patients with baseline left ventricular dysfunction and suspected coronary disease who develop PEA should be evaluated for acute coronary occlusion.

A right ventricular state of mind in the progression of heart failure with reduced ejection fraction: implications for left ventricular assist device therapy.

Right ventricular (RV) function in patients with preexisting left ventricular (LV) systolic dysfunction is key to determining prognosis and identifying appropriate candidates for cardiac replacement therapy. This becomes particularly relevant during selection for left ventricular assist device (LVAD) therapy, since adequate cardiac output, differently from heart transplantation, still relies on native RV function. Importantly, accumulating evidence indicates that RV failure (RVF) carries detrimental consequences of progressive end-organ dysfunction due to systemic venous congestion-mediated inflammation and oxidative stress. Therefore, it is crucial to detect RVF early on in the disease state through heightened clinical suspicion and noninvasive and/or invasive modalities before the RV fails and organ damage ensues, precluding patients from life saving measures such as LVAD therapy. The purpose of this review is to discuss the pathogenesis of RVF, its systemic consequences, implications for pre- and post-LVAD management, and its impact on clinical outcomes.

603 Comparison of Surgical and Transcatheter Edge-to-Edge Mitral Valve Repair in Patients With Left Ventricular Dysfunction

A comparison of minimally invasive mitral valve repair (MIMVR) and transcatheter edge-to-edge repair (TMVR) on ventricular remodelling in patients with pre-existing left ventricular systolic dysfunction (LVEF≤50%) has not previously been reported. This study compares the immediate and short-term echocardiographic outcomes of MIMVR and TMVR. This is a single-center, retrospective, observational cohort study of patients with an LVEF≤50% who underwent MIMVR or TMVR between February 2008-August 2018. Baseline and postoperative TTE’s (pre-discharge; 3 months) were analysed by two-blinded independent investigators. Eighty-three patients (33 MIMVR; 50 TMVR; 76 [19] years) with grade 3-4 MR and an LVEF≤50% underwent MIMVR or TMVR. Less than 2+MR was achieved in 97% of MIMVR patients with a corresponding reduction in LVEDVI (Pre-70±23mLs/m2; Post-53mLs±17mLs/m2; p<0.01). Ninety-two percent of TMVR patients had ≤2+MR pre-discharge, albeit with no significant post-procedural reduction in LVEDVI (Pre-81±43mLs/m2; Post-81±42mLs/m2; p=0.52). At 3-months in the TMVR cohort, ≤1+MR remained in 71% of patients whilst 10% had ≥3+MR. There was a transient decline in LVEF in both cohorts, however this recovered to baseline at 3-months. Both cohorts demonstrated a reduction in pulmonary artery systolic pressure at 3-months (MIMVR post-28±7mmHg, p=0.13; TMVR post-41±16mmHg, p<0.01) and a trend towards improved RVFAC albeit not statistically significant. Surgical MIMVR is more effective than TMVR in correcting MR and reducing LV volumes in patients with pre-existing LV dysfunction. These findings raise the possibility that valve annuloplasty, in addition to repair, is an important component of remodelling and may help to guide future transcatheter device selection.

Impact of Arterial Hypertension on Doxorubicin-Based Chemotherapy-Induced Subclinical Cardiac Damage in Breast Cancer Patients.

Advances in oncologic therapies have allowed to achieve better outcomes and longer survival in many patients with breast cancer. Anthracyclines are cytotoxic antibiotics widely used in daily oncology practice. However, anthracyclines cause cardiotoxicity which is a limiting factor of its use. Cumulative dose of anthracyclines is the major cause of induced cardiotoxicity. According to previous clinical trials, the major predisposing high-risk factors for anthracycline-based chemotherapy-induced cardiotoxicity are age, body weight, female gender, radiotherapy, and other diseases such as diabetes and hypertension. Experimental studies in animals confirm that hypertension may be a significant factor predisposing anthracycline-based chemotherapy cardiotoxicity. The main objective of our study was to identify the effect of pre-existing arterial hypertension on the development of subclinical cardiac damage during or after doxorubicin-based chemotherapy in breast cancer patients. The study was performed prospectively between March 2016 and January 2017 in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics Department of Oncology and Department of Cardiology. Data of 73 women with breast cancer treated with doxorubicin-based chemotherapy in outpatient clinic were analyzed. Statistically significant association between pre-existing arterial hypertension and left ventricular systolic dysfunction after completion of chemotherapy was observed (P < 0.004). Our study demonstrated that pre-existing arterial hypertension has a very important role in the development of anthracycline-based chemotherapy-induced cardiotoxicity, despite arterial hypertension control quality. Consequently, further studies evaluating impact of other risk factors and how early and sufficient management of arterial hypertension could influence the development of cardiotoxicity are needed to avoid permanent cardiac damage.

Use of 65 cm large caliber Dryseal sheaths to facilitate delivery of the Edwards SAPIEN valve to dysfunctional right ventricular outflow tracts.

The Edwards SAPIEN valve and its delivery system may complicate transit through the right heart during transcatheter pulmonary valve replacement (tPVR). We report our early experience using a large diameter, 65 cm delivery sheath to facilitate delivery of the SAPIEN valve to the right ventricular outflow tract (RVOT). Retrospective analysis of all patients from three large congenital heart centers undergoing tPVR with the Edwards SAPIEN valve delivered with the 65 cm Gore Dryseal Sheath. Over a 12 month period, 30 patients (17 female) with median age 17.5 years (range 8-72) underwent attempted tPVR with the SAPIEN valve delivered using the 65 cm Dryseal sheath (20-26Fr). All procedures resulted in successful valve delivery to the target area. Twenty patients had a native RVOT. The most commonly used valve diameter was 29 mm (n = 15) with the majority of cases requiring a 26Fr Dryseal sheath (n = 20). One patient with severe RVOT stenosis underwent prestenting. Median procedure time was 100 min (59-225). No patient had increase in tricuspid valve regurgitation as a consequence of valve delivery. One patient required a synchronous cardioversion for intraprocedural VT and another required ECMO postprocedure due to severe pre-existing left ventricular dysfunction. On median follow-up of 5 months, all patients had mild or less pulmonary regurgitation. Median peak Doppler velocity across the pulmonary valve was 2.2 m/s (1.7-4). There were no clinically relevant complications relating to vascular access. Using 65 cm Dryseal sheaths facilitates delivery of SAPIEN valves in patients with dysfunctional RVOTs.

Precardiogenic Shock: A New Clinical Entity.

The pathogenesis of cardiogenic shock (CS) has evolved from an acute event due to a large myocardial infarction to a semiacute event due to rapid hemodynamic deterioration on a background of preexisting left ventricular systolic dysfunction. Pre-CS refers to the period of rapid hemodynamic deterioration that precedes overt CS with hypotension, inflammatory response, and end-organ failure. Mortality remains extremely high in CS and has not improved over the past decades. Pre-CS offers a unique opportunity to initiate early treatment that may result in better clinical outcomes. The present review addresses the definition, recognition, and management of pre-CS with the pharmacologic or mechanical support of the failing left ventricle.

Risk factors for chemotherapy-related cardiac toxicity.

The purpose of this review is to discuss the clinical and treatment-related factors that increase the risk of cardiotoxicity with anthracyclines and human epidermal growth factor 2 receptor inhibitors. Age and preexisting left ventricular dysfunction have been identified most consistently as being associated with the development of clinical heart failure or a worsening of left ventricular function with chemotherapy. Other cardiovascular conditions, including hypertension, diabetes, and coronary artery disease, are also associated with the risk of cardiotoxicity. There is growing evidence that Blacks are at a higher risk of developing cardiotoxicity than Whites, even after adjusting for known confounders. Pharmacogenomics is also emerging as a potential tool to help identify patients who are at higher risk for cardiotoxicity. Treatment-related risk factors include the dose of anthracycline or its formulation, whether the patient is receiving additional chemotherapeutic agents or radiation. Several clinical and treatment-related risk factors are associated with cardiotoxicity. Further study is needed to determine whether optimization of modifiable risk factors prior to treatment can reduce the risk of cardiotoxicity.