Decrease In Left Ventricular Ejection Fraction Research Articles

Prognostic role of cardiac magnetic resonance in left ventricular noncompaction

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with a wide phenotypic expression. Risk factors have not been well established and prognostic stratification remains challenging. Purpose Describe prognostic role of CMR on long term outcomes of LVNC patients. Methods Retrospective multicentric longitudinal cohort study of consecutive patients fulfilling imaging diagnostic criteria for LVNC (Jenni echo criteria and Petersen and Jacquier CMR criteria). Demographic, ECG, genetic, family and treatment variables were recorded. Baseline CMR was used for the analysis. LV ejection fraction (LVEF) was categorized according to heart failure (HF) guidelines and late gadolinium enhancement (LGE) was visually assessed in a binary way. End points were HF, ventricular arrhythmias (VA), systemic embolisms (SE) and all-cause death. Major adverse cardiovascular events (MACE) were the combination of the four previous end points. In patients with initially preserved LVEF (≥ 50%), LV adverse remodelling (LVAR) was defined as an LVEF < 50% and/or absolute decrease of ≥10% in LVEF at last follow-up. Results 585 patients from 12 referral centres were included from 2000 to 2018. Age at diagnosis was 45 ± 20 years, 334 (57%) were male, baseline LVEF was 48 ± 17% and 18% presented LGE. During a median follow-up of 5.1 years (IQR 2.3-8.1), 110 (19%) patients presented HF, 87 (15%) VA, 18 (3%) SE and 34 (6%) died. MACE occurred in 223 (38%) patients. LVEF was independently associated with HF, VA, SE and MACE: HR were 1.08, 1.02, 1.04 and 1.02 respectively (all p < 0.05). LGE was more frequent in patients with reduced LVEF (39 Vs 53%, p < 0.001) and was associated with higher HF and VA risk in patients with an LVEF > 35% (HR 2.69 and 2.48 respectively, p < 0.05) (Figure 1). No MACE (0%) occurred during long-term follow-up in patients with preserved LVEF, no LGE as well as no ECG abnormalities and no family aggregation. 305 (52%) patients presented with initially preserved LVEF, and 230 (75%) of those had LVEF available at last follow-up. LVAR occurred in 50 (22%) patients: 22 (10%) had an LVEF < 50% and 41 (18%) an absolute ≥ 10% decrease in LVEF. LGE was independently associated with LVAR (HR 3.51, p = 0.045) (Figure 2). Conclusions Cardiac magnetic resonance has an important prognostic role in LVNC. LVEF is the most powerful predictor of events. Myocardial fibrosis is associated with worse outcomes in patients without severe systolic dysfunction, as well as with left ventricular adverse remodelling in those with initially preserved LVEF. Besides, CMR may identify a low-risk subgroup of LVNC patients. Therefore, CMR should be used in risk stratification in LVNC.

Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study.

BackgroundThe CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS).MethodsIn this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed.ResultsBetween Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%).ConclusionAt 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity.Trial Registration Number ClinicalTrials.gov reference NCT00563953.

Predictors of the Use of Mineralocorticoid Receptor Antagonists in Patients With Left Ventricular Dysfunction Post-ST-Segment-Elevation Myocardial Infarction.

BackgroundGuidelines recommend mineralocorticoid receptor antagonist (MRA) use in patients with left ventricular ejection fraction ≤40% following a myocardial infarction plus heart failure or diabetes mellitus, based on mortality benefit in the EPHESUS (Eplerenone Post‐Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial. The objective of this study was to evaluate the real‐world utilization of MRAs for patients with ST‐segment–elevation myocardial infarction (STEMI) with left ventricular dysfunction.Methods and ResultsThe prospective, population‐based, Vancouver Coastal Health Authority STEMI database was linked with local outpatient cardiology records from 2007 to 2018. EPHESUS criteria were used to define post‐STEMI MRA eligibility (left ventricular ejection fraction ≤40% plus clinical heart failure or diabetes mellitus, and no dialysis‐dependent renal dysfunction). The primary outcome was MRA prescription among eligible patients at discharge and the secondary outcome was MRA prescription within 3 months postdischarge. Of 2691 patients with STEMI, 317 (12%) were MRA eligible, and 70 (22%) eligible patients were prescribed an MRA at discharge. Among eligible patients with no MRA at discharge, 12/126 (9.5%) with documented postdischarge follow‐up were prescribed an MRA within 3 months. In multivariable analysis, left ventricular ejection fraction (odds ratio [OR], 1.55 per 5% left ventricular ejection fraction decrease; 95% CI, 1.26–1.90) and calendar year (OR, 1.23 per year, 95% CI, 1.11–1.37) were associated with MRA prescription at discharge. Other prespecified variables were not associated with MRA prescription.ConclusionsIn this contemporary STEMI cohort, only 1 in 4 MRA‐eligible patients were prescribed an MRA within 3 months following hospitalization despite high‐quality evidence for use. Novel decision‐support tools are required to optimize pharmacotherapy decisions during hospitalization and follow‐up to target this gap in post‐STEMI care.

Changes in Left Ventricular Ejection Fraction after Mitral Valve Repair for Primary Mitral Regurgitation.

This study sought to identify the short- and long-term changes in left ventricular ejection fraction (LVEF) after mitral valve repair (MVr) in patients with chronic primary mitral regurgitation according to preoperative LVEF (pre-LVEF) and preoperative left ventricular end-systolic diameter (pre-LVESD). This study evaluated 461 patients. Restricted cubic spline regression models were constructed to demonstrate the long-term changes in postoperative LVEF (post-LVEF). The patients were divided into four groups according to pre-LVEF (<50%, 50–60%, 60–70%, and ≥70%). The higher the pre-LVEF was, the greater was the decrease in LVEF immediately after MVr. In the same pre-LVEF range, immediate post-LVEF was lower in patients with pre-LVESD ≥ 40 mm than in those with pre-LVESD < 40 mm. The patterns of long-term changes in post-LVEF differed according to pre-LVEF (p for interaction < 0.001). The long-term post-LVEF reached a plateau of approximately 60% when the pre-LVEF was ≥50%, but it seemed to show a downward trend after reaching a peak at approximately 3–4 years after MVr when the pre-LVEF was ≥70%. The patterns of short- and long-term changes in post-LVEF differed according to pre-LVEF and pre-LVESD values in patients with chronic primary mitral regurgitation after MVr.

Cardiac Dysfunction in a Mouse Vascular Dementia Model of Bilateral Common Carotid Artery Stenosis.

Background: Cardiac function is associated with cognitive function. Previously, we found that stroke and traumatic brain injury evoke cardiac dysfunction in mice. In this study, we investigate whether bilateral common carotid artery stenosis (BCAS), a model that induces vascular dementia (VaD) in mice, induces cardiac dysfunction.Methods: Late-adult (6–8 months) C57BL/6J mice were subjected to sham surgery (n = 6) or BCAS (n = 8). BCAS was performed by applying microcoils (0.16 mm internal diameter) around both common carotid arteries. Cerebral blood flow and cognitive function tests were performed 21–28 days post-BCAS. Echocardiography was conducted in conscious mice 29 days after BCAS. Mice were sacrificed 30 days after BCAS. Heart tissues were isolated for immunohistochemical evaluation and real-time PCR assay.Results: Compared to sham mice, BCAS in mice significantly induced cerebral hypoperfusion and cognitive dysfunction, increased cardiac hypertrophy, as indicated by the increased heart weight and the ratio of heart weight/body weight, and induced cardiac dysfunction and left ventricular (LV) enlargement, indicated by a decreased LV ejection fraction (LVEF) and LV fractional shortening (LVFS), increased LV dimension (LVD), and increased LV mass. Cognitive deficits significantly correlated with cardiac deficits. BCAS mice also exhibited significantly increased cardiac fibrosis, increased oxidative stress, as indicated by 4-hydroxynonenal and NADPH oxidase-2, increased leukocyte and macrophage infiltration into the heart, and increased cardiac interleukin-6 and thrombin gene expression.Conclusions: BCAS in mice without primary cardiac disease provokes cardiac dysfunction, which, in part, may be mediated by increased inflammation and oxidative stress.

Beta-Blocker Use Is Associated With Prevention of Left Ventricular Remodeling in Recovered Dilated Cardiomyopathy.

BackgroundWithdrawal of optimal medical therapy has been reported to relapse cardiac dysfunction in patients with dilated cardiomyopathy (DCM) whose cardiac function had improved. However, it is unknown whether beta‐blockers can prevent deterioration of cardiac function in those patients. We examined the effect of beta‐blockers on left ventricular ejection fraction (LVEF) in recovered DCM.Methods and ResultsWe analyzed the clinical personal record of DCM, a national database of the Japanese Ministry of Health, Labor and Welfare, between 2003 and 2014. Recovered DCM was defined as a previously documented LVEF <40% and a current LVEF ≥40%. Patients with recovered DCM were divided into 2 groups according to the use of beta‐blockers. A one‐to‐one propensity case‐matched analysis was used. The primary outcome was defined as a decrease in LVEF >10% at 2 years of follow‐up. Of 5370 eligible patients, 4104 received beta‐blockers. Propensity score matching yielded 1087 pairs. Mean age was 61.9 years, and 1619 (74.5%) were men. Mean LVEF was 49.3±8.2%, and median B‐type natriuretic peptide was 46.6 (interquartile range, 18.0–118.1) pg/mL. The primary outcome was observed less frequently in the beta‐blocker group than in the no‐beta‐blocker group (19.6% versus 24.0%; odds ratio [OR], 0.77; 95% CI, 0.63–0.95; P=0.013). Subgroup analysis demonstrated that female patients (women: OR, 0.54; 95% CI, 0.36–0.81; men: OR, 0.88; 95% CI, 0.69–1.12; P for interaction=0.040) were benefited by beta‐blockers.ConclusionsBeta‐blocker use could prevent deterioration of left ventricular systolic function in patients with recovered DCM.

Abstract MP27: Changes In Cardiac Structure And Function Over 25 Years Are Associated With Lower Midlife Cognition: The Cardia Study

Background: Cardiovascular risk factors are associated with worse cognition, yet much less is known about the association of cardiac structure and function and decline over time with cognitive function, even as early as midlife. Method: We included 2256 subjects from the CARDIA (Coronary Artery Risk Development in Young Adults) study (60% women, 44% black). Echocardiograms were repeated at Years 5, 25, 30 (mean age 30, 50, 55 years, respectively) to assess left ventricular (LV) mass (LVM); LV systolic function with LV ejection fraction (LVEF); LV diastolic function with left atrial volume (LAV) and early peak mitral velocity (E)/early peak mitral annular velocity (e’) ratio. Five cognitive domains were assessed at Year 30: verbal memory, verbal fluency, processing speed, executive function, and global cognition. We investigated the association of (1) 25-year change and (2) Year 25 cardiac structure and function on midlife cognition using linear regressions. Results: Over 25 years, LVM and LAV increased with mean change (SD) of 5.7 g/m 2 (21.7) and 9.6 mL/m 2 (7.4) while LVEF decreased by mean (SD) change of 1.5% (9.0). Greater 25-year increase in LVM was associated with lower global cognition, processing speed, executive function, verbal memory, and verbal fluency. Similarly, greater 25-year increase in LAV was associated with lower cognition on most cognitive domains. Adjustment for (1) demographics, education and (2) hypertension, diabetes, smoking did not notably change the results. 25-year decrease in LVEF was not associated with cognition. In addition, higher Year 25 LVM, LAV and E/e’ ratio were significantly associated with worse cognition on most cognitive domains. Conclusion: Midlife altered cardiac structure and adverse changes from early to middle adulthood are associated with lower midlife cognition. Moreover, LV diastolic but not systolic dysfunction is linked to lower cognition. Our results provide novel information linking early to midlife cardiac structure and function to cognition.

Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab (P+T) in the APHINITY trial.

510 Background: Trastuzumab (T) increases the incidence of cardiac events (CEs) in patients (pts) with early breast cancer (BC). Dual blockade with P+T improves BC outcomes and is the standard of care for high-risk HER2-positive BC pts following the phase 3 APHINITY trial that evaluated the addition of P or placebo (Pla) to T and chemotherapy (CT). We analyzed the cardiac safety of P+T in APHINITY. Methods: APHINITY eligibility required a left ventricular ejection fraction (LVEF) ≥55% at study entry. LVEF assessment was performed every 3 months (mos) during treatment, every 6 mos up to month 36, and yearly thereafter. Primary CE was defined as heart failure (HF) class III/IV and a significant decrease in LVEF of at least 10 percentage points from baseline and to &lt;50%, or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF or CEs confirmed by the cardiac advisory board. Results: The safety analysis population consists of 4,769 pts. With 74 mos median follow-up (FU), CEs were observed in 159 pts (3.3%): 83 (3.5%) in the P+T and 76 (3.2%) in Pla+T arms, respectively. Most CEs occurred during anti-HER2 therapy: 123/159 (77.4%) and were asymptomatic or mildly symptomatic LVEF decrease (133/159; 83.6%) (Table 1). There were 2 cardiac deaths in each arm (0.1%). More CEs occurred in pts receiving an anthracycline-based CT compared to those receiving non-anthracycline CT (139 vs. 20 CEs, respectively). Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 pts (81.9%). Conclusions: Dual blockade with P+T does not increase the risk of CE compared to Pla+T alone. The use of anthracycline-based CT increases the risk of a CE; hence non-anthracycline CT may be considered particularly in pts with other cardiovascular risk factors. Clinical trial information: NCT01358877. [Table: see text]

Lisinopril or carvedilol in prevention of trastuzumab-induced cardiotoxicity in patients with HER2-positive early stage breast cancer: Longitudinal changes of left ventricular ejection fraction below normal levels (LVEF &lt;50%).

509 Background: Treatment of HER2-positive breast cancer patients with trastuzumab is highly effective. However, a trastuzumab-associated decline in the left ventricular ejection fraction (LVEF) and clinical heart failure often prompt interruption and discontinuation of treatment. We therefore evaluated the preventive impact of an ACE inhibitor or beta blockers on the left ventricular ejection fraction (LVEF) during treatment of trastuzumab and chemotherapy. Methods: In a prospective randomized study, women with early stage HER2 positive breast cancer undergoing (neo)adjuvant chemotherapy with trastuzumab were randomized to receive either once daily lisinopril (10mg), carvedilol (10mg) or placebo during treatment with trastuzumab and further stratified by anthracycline use (AC+T versus nonAC+T). In a follow up to the initially presented primary endpoint of overall cardiotoxicity, we measured the protective effects of lisinopril or carvedilol to prevent a trastuzumab induced LVEF decrease to less than 50% over the course of therapy as well as the impact on LVEF decrease by &gt;10% within normal LVEF levels. Results: A total of 468 women (mean age was 51±10.7 years) with HER2 overexpressing early-stage breast cancer from 127 community-based oncology practices were enrolled, a prespecified minimum target of 189 (40%) patients were treated with AC+T and 279 (60%) with nonAC+T. Baseline cardiac risk factors of this study population included obesity and an elevated blood pressure. Patients in the anthracycline group were younger and without hypertension. A small, not clinically relevant decrease in LVEF was observed during trastuzumab therapy in all patients which was not significantly altered by any of the cardiac interventions. The rate of LVEF decline to &lt;50% was much more frequent in patients treated with an anthracycline than those with a non-anthracycline containing regimen (21% vs 4.1%). Treatment with lisinopril averted the decline in LVEF in the AC+T group compared to placebo (10.8% vs 30.5%, p=0.045). A smaller but not significant effect was seen by carvedilol. The incidence of cardiotoxicity manifesting as LVEF decrease by ≥10% within the normal range was similar in both AC+T and the nonAC+T arms, and not affected by either lisinopril or carvedilol. Conclusions: In patients treated with trastuzumab without anthracyclines, the impact of trastuzumab on LVEF is small and infrequent. In contrast, patients treated with anthracyclines prior to trastuzumab, demonstrated a decrease in LVEF to below normal levels in a larger than previously reported number of women in this community based setting. The trastuzumab-anthracycline induced decline in LVEF could be prevented with concurrent treatment with lisinopril, which was tolerable even in patients without hypertension. Clinical trial information: NCT01009918.

Evaluation of cardiotoxicity related to cancer treatment in an urban safety-net hospital.

e18804 Background: Improvements in survival of cancer patients has led to an increased awareness of the long-term cardiac effects of chemotherapy. American Society of Clinical Oncology (ASCO) Clinical Practice Guideline emphasizes the needs of identifying patients with higher risk for cardiovascular toxicity prior to treatment initiation. African American (AA) race has been associated with higher incidence of cardiotoxicity and resultant incomplete adjuvant therapy compared to white patients. Here, we investigate the utilization of various imaging modalities to monitor chemotherapy-induced cardiotoxicity in a predominantly AA breast cancer population at the safety-net hospital. Methods: This study was a retrospective analysis of breast cancer patients (n = 33) who received trastuzumab, doxorubicin, and/or paclitaxel between year 2018 and 2020 at the safety-net hospital in Atlanta, Georgia. Patient demographics, clinical characteristics, pathologic variables as well as utilization of echocardiography, echocardiography with global longitudinal strain (GLS), and multigated acquisition scans (MUGA). Results: The majority of patients were AA female (27/33, 81.8%) and the mean age at diagnosis was 52 ± 13.2 years. 11/33 (33%), 24/33 (72.7%), and 20/33 (33.3%) were treated with trastuzumab, paclitaxel, and doxorubicin respectively. Baseline left ventricular ejection fraction (LVEF) was assessed in 32/33 (96.7%) of patients: MUGA 21/32 (65.6%), echocardiography 10/33 (31.3%), and echocardiography with GLS 1/32 (3.1%). 13/32 (40.6%) patients underwent repeated imaging, with the average time between repeat MUGA and echocardiography being 254.3 and 147 days respectively. LVEF decrease of &gt; 10% was noted in 4 patients with repeat MUGA but in none of the repeat echocardiography group. Only 5 patients had echocardiography with GLS over the study period, of which 2/5 (40%) had a drop in GLS in the setting of normal ejection fraction, consistent with occult LV systolic dysfunction. Conclusions: Our study suggests that African American patients at a safety net hospital receive the equivalent level of cardiac surveillance during cancer treatment. However, GLS imaging is underutilized in the detection of subclinical cardiac dysfunction in breast cancer patients receiving chemotherapy. Larger, long terms prospective studies are needed to assess the implications of abnormal GLS and progression to clinical left ventricular systolic dysfunction in the AA breast cancer population.

CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

BackgroundThe CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts.ObjectivesThis study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment.MethodsWe recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA).ResultsBreast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups.ConclusionsCBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study.

This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex. Biomarkers and echocardiographic measures were measured at both baseline and follow-up in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders. Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %. Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.

Prevalence and predictors of pacing-induced cardiomyopathy in young adult patients (

Clinical trials and observational studies of pacing-induced cardiomyopathy (PICM) have largely included elderly patients with mean age >70 years. The prevalence and predictors of PICM in younger patients (age < 60 years) after pacemaker implantation are not known. Adults (18-59 years) who received single-chamber ventricular or dual-chamber pacemakers at Vanderbilt University Medical Center from 1986 to 2015 were included. Patients without documented ventricular pacing burden and patients with baseline left ventricular ejection fraction (LVEF) <35% were excluded. PICM was defined as LVEF decrease of ≥ 10% and LVEF < 50% during follow-up with right ventricular pacing ≥20%, and without alternative explanations for cardiomyopathy. A total of 325 patients were included in the study. During a median follow-up duration of 11.5 (Interquartile range 7-17) years, 38 patients (11.7%) developed PICM (1.3 per 100 patient-year). Older age (HR 2.5 for age ≥50 years, p = .013), reduced baseline LVEF (HR 2.4, p = .022), and preimplant AVB (HR 2.7, p = .007) were associated with an increased risk of PICM in the multivariate analysis. Furthermore, baseline AF conferred an increased risk of PICM only in patients without preimplant AVB but not patients with pre-implant AVB. The incidence of PICM in young patients was low, but PICM could occur more than a decade after pacemaker implantation. Older age, baseline reduced LVEF, and preimplant AVB were associated with an increased risk of PICM in the young patient cohort.

April 2021 at a glance: focus on systolic function, quality of life and treatment in heart failure.

Left ventricular (LV) systolic ejection time is a prognostic marker in patients with heart failure (HF) and reduced ejection fraction (HFrEF).1, 2 Alhakak et al.3 reviewed the definition and methods of measurement of LV ejection time, the mechanisms behind its shortening in HFrEF, its role as a prognostic marker and in the assessment of the response to medical treatment. Left ventricular ejection fraction (LVEF) remains the landmark parameter of LV systolic function. It is a major prognostic marker both in acute and chronic HF.4, 5 Strange et al.5, 6 furthered their previous findings showing in a large cohort of 117 275 subjects followed up by echocardiography that even modest LVEF changes over time, i.e. at least 6 months, have a significant prognostic impact. Five-year all-cause mortality increased from 12% to 29% among subjects with the smallest to the largest decrease in LVEF (from <5 units to >30 units). Health-related quality of life (QoL) scores are clinically relevant in patients with HF.7-9 In a recent analysis of BIOSTAT-CHF, Ravera et al.10 reported worse QoL scores in women with HFrEF as compared with men, both when assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score (median 44 vs. 53; P < 0.001) and the EuroQol 5 dimensions utility score (median 0.62 vs. 0.73; P < 0.001). Of note, QoL was independently associated with subsequent outcome both in women and men. Turgeon et al.11 synthetized evidence regarding the impact of HFrEF pharmacotherapy on QoL in a comprehensive systematic review and meta-analysis. QoL was improved by angiotensin receptor blockers, angiotensin receptor–neprilysin inhibitor, sodium–glucose co-transporter 2 inhibitors, ivabradine, hydralazine–nitrate, and intravenous iron whereas findings were inconclusive for angiotensin-converting enzyme inhibitors, beta-blockers, digoxin, and oral iron. Sodium–glucose co-transporter 2 inhibitors have a pivotal role in the treatment of patients with HFrEF.12-14 Their cost-effectiveness has also been shown.15 Despite differences in the pathophysiology of ischaemic and non-ischaemic HF,16 dapagliflozin had similar effects on the risk of worsening HF or cardiovascular death as well as on symptoms and QoL in patients with HFrEF of ischaemic and non-ischaemic aetiology in DAPA-HF.17 Comorbidities have a major role in patients with HF, including those enrolled in clinical trials.18 Two analyses from DAPA-HF reported that patients with concomitant anaemia or chronic obstructive pulmonary disease had poorer outcomes. However, the benefit of dapagliflozin on cardiovascular events was independent of their presence.19, 20 Rivaroxaban 2.5 mg twice daily may be considered among treatment options for patients with HF, coronary artery disease and LVEF >30%.14 An analysis of COMMANDER-HF demonstrated that high plasma D-dimer levels (>515 ng/mL) identify patients at high risk of stroke who can benefit from rivaroxaban administration.21 Iron deficiency is a major therapeutic target in HF.9, 14, 22 In a non-randomized, open-label, prospective pilot study, oral sucrosomial iron improved exercise capacity and QoL in patients with HFrEF and Iron deficiency, with significant improvement in 6-min walk distance and KCCQ at 3 and 6 months (all adjusted P-values <0.01).23 The MSC-HF trial reported a positive effect of intramyocardial injection of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in patients with ischaemic HF.24 The Phase II CONCERT-HF trial demonstrated that the combination of MSCs and c-kit positive cardiac cells was associated with further improvement in clinical outcome and QoL.25

Change in ejection fraction and long-term mortality in adults referred for echocardiography.

We investigated long-term mortality associated with changes in left ventricular ejection fraction (LVEF) in a large, real-world patient cohort. A total of 117 275 adults (63 ± 16 years, 46% women) had LVEF quantified by the same method ≥6months apart. This included 17 343 cases (66 ± 15 years, 48% women) being initially investigated for heart failure (HF). During 3.3 [interquartile range (IQR) 1.7-6.0] years from first to last echocardiogram, median change in LVEF was -1 (IQR -8 to +5) units from a baseline of 62% (IQR 54-69%). During subsequent 7.6 (IQR 4.3-10.1) years of follow-up, 11 397 (9.7%) and 34 101 (29.1%) cases died from cardiovascular disease and all causes, respectively. Actual 5-year, all-cause mortality increased from 12% to 29% among those with the smallest to the largest decrease in LVEF (from <5units to >30 units); the adjusted risk of cardiovascular-related mortality increased two- to eightfold beyond a >10-unit decline in LVEF (vs. minimal change; P< 0.001 for all comparisons). Among those initially investigated for HF (32% with initial LVEF <50%), the adjusted hazard ratio for cardiovascular-related mortality ranged from 0.35 [95% confidence interval (CI) 0.28-0.49] to 4.21 (95% CI 3.30-5.22) for a >30-unit increase to >30-unit decline in LVEF (vs. minimal change; P< 0.001 for both comparisons). A distinctive, bi-directional plateau of improved vs. worsening mortality was evident around a final LVEF of 50% to 55%. These data, derived from a large, heterogeneous cohort of adults being followed up with echocardiography, suggest that modest LVEF changes (particularly around an LVEF of 50-55%) may be of clinical significance.

Improved Cardiac Outcomes by Early Treatment with Angiotensin-Converting Enzyme Inhibitors in Becker Muscular Dystrophy.

Background:The latest practice guidelines from the American College of Cardiology/American Heart Association recommend the prescription of an ACE-i for patients presenting with non-ischemic cardiomyopathy when left ventricular ejection fraction (LVEF) falls below 40%.Objective:To determine if the initiation of treatment with an angiotensin-converting enzyme inhibitor (ACE-i) earlier than recommended by practice guidelines issued by professional societies improves the long-term cardiac outcomes of patients presenting with Becker muscular dystrophy (MD) cardiomyopathy.Methods:From a multicenter registry of Becker MD, we selected retrospectively patients presenting between January 1990 and April 2019 with a LVEF ≥40 and ≤49%. We used a propensity score analysis to compare the risk of a) hospitalization for management of heart failure (HF), and b) a decrease in LVEF to <35% in patients who received an ACE-i when LVEF fell below 40% (conventional treatment), versus below 50% (early treatment).Results:From the 183 patients entered in our registry, we identified 85 whose LVEF was between 40 and 49%, 51 of whom received early and 34 received conventional ACE-i treatment. Among patients with early versus conventional treatments, 2 (3.9%) versus 4 (11.8%) were hospitalized for management of HF [hazard ratio (HR) 0.151; 95% confidence interval (CI) 0.028 to 0.822; p = 0.029], and 9 (17.6%) versus 10 (29.4%) had a decrease in LVEF below 35% (HR 0.290; 95% CI 0.121 to 0.694; p = 0.005).Conclusions:The long-term cardiac outcome of patients presenting with Becker MD was significantly better when treatment with ACE-i was introduced after a decrease in LVEF below 50%, instead of below 40% as recommended in the current practice guidelines issued by professional societies.

Association du double blocage de HER2 et radiothérapie dans la prise en charge du cancer du sein exprimant HER2

PurposeThe tolerance of the concurrent use of radiotherapy, pertuzumab and trastuzumab is unknown. The purpose of this study was to evaluate the toxicity of this association in patients treated for HER2 positive metastatic and/or locally recurrent unrespectable breast cancer. Material and methodsA retrospective study was performed in our institution for all consecutive patients treated with concurrent irradiation, pertuzumab and trastuzumab. The radiotherapy was performed while pertuzumab and trastuzumab were administrated as a maintenance treatment at the dose of 420mg (total dose) and 6mg/kg respectively every 3 weeks without chemotherapy. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Left ventricular ejection fraction (LVEF) was measured at baseline and then every 3–4 months. ResultsWe studied 77 patients. treated in between 2013 and 2019 with median follow-up of 38 months (range 0–264 months). Median age was 53 years (33–86). There were 50 patients (64.9%) with metastatic and 27 patients (35.1%) with recurrent disease. All patients received docetaxel followed by P–T as first line treatment and they received 34 cycles (10–85) of pertuzumab and trastuzumab. All patients experienced partial or complete response according to RECIST criteria. Irradiation volumes were whole breast (41 patients, 53.2%) and chest wall (29 patients, 37.7%) at a dose of 50Gy with a median duration of 39 days. Radiotherapy of lymph nodes was performed in 53 patients (68.8%) as following: supraclavicular–infraclavicular and axillary lymph nodes in 52 patients (67.5%), and internal mammary nodes in 31 patients (40.3%). For 20 patients. (26.0%) radiotherapy was palliative: bone irradiation (12 patients, 15.6%), whole-brain radiotherapy (2 patients, 2.6%), cerebral metastasis irradiation (6 patients). As early toxicity we observed: radio dermatitis as following: 36 patients (46.8%) presented grade I, 17 patients (22.1%) presented grade II, and 3 patients (3.9%) presented grade III. One patient (1.3%) presented grade II esophagitis. One patient (1.3%) presented asymptomatic decrease of LVEF during treatment and 6 patients (7.7%) presented a decrease of LVEF. There was no radiation-induced pneumonitis. As late toxicity, we observed 1 (1.3%) case of grade I and 1 (1.3%) with grade II telangiectasia. There was 1 case (1.3%) of grade III cardiac toxicity, 8 months after the concurrent treatment. ConclusionThe concurrent use of radiotherapy, pertuzumab and trastuzumab is feasible with good tolerance. Larger prospective data with longer follow-up is needed to confirm these results.

Association of Left Ventricular Systolic Function With Incident Heart Failure in Late Life

Limited data exist regarding the association of subtle subclinical systolic dysfunction and incident heart failure (HF) in late life. To assess the independent associations of subclinical impairments in systolic performance with incident HF in late life. This study was a time-to-event analysis of participants without heart failure in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, community-based cohort study, who underwent protocol echocardiography at the fifth study visit (January 1, 2011, to December 31, 2013). Findings were validated independently in participants in the Copenhagen City Heart Study (CCHS). Data analysis was performed from June 1, 2018, to February 28, 2020. Left ventricular ejection fraction (LVEF), longitudinal strain (LS), and circumferential strain (CS) measured by 2-dimensional and strain echocardiography. Main outcomes were incident adjudicated HF and HF with preserved and reduced LVEF at a median follow-up of 5.5 years (interquartile range, 5.0-5.8 years). Cox proportional hazards regression models adjusted for demographics, hypertension, diabetes, obesity, smoking, coronary disease, estimated glomerular filtration rate, LV mass index, e', E/e', and left atrial volume index. Lower 10th percentile limits were determined in 374 participants free of cardiovascular disease or risk factors. Among 4960 ARIC participants (mean [SD] age, 75 [5] years; 2933 [59.0%] female; 965 [19%] Black), LVEF was less than 50% in only 76 (1.5%). In the 3552 participants with complete assessment of LVEF, LS, and CS, 983 (27.7%) had 1 or more of the following findings: LVEF less than 60%, LS less than 16.0%, or CS less than 23.7%. Modeled continuously or dichotomized, worse LVEF, LS, and CS were each independently associated with incident HF. The adjusted hazard ratio (HR) per SD decrease in LVEF was 1.41 (95% CI, 1.29-1.55); the HR for LVEF less than 60% was 2.59 (95% CI, 1.99-3.37). Similar findings were observed for continuous LS (HR, 1.37; 95% CI, 1.22-1.53) and dichotomized LS (HR, 1.93; 95% CI, 1.46-2.55) and for continuous CS (HR, 1.39; 95% CI, 1.22-1.57) and dichotomized CS (HR, 2.30; 95% CI, 1.64-3.22). Although the magnitude of risk for incident HF or death associated with impaired LVEF was greater using guideline (HR, 2.99; 95% CI, 2.19-4.09) compared with ARIC-based limits (HR, 1.88; 95% CI, 1.58-2.25), the number of participants classified as impaired was less (104 [2.1%] based on guideline thresholds compared with 692 [13.9%] based on LVEF <60%). The population-attributable risk associated with LVEF less than 60% was 11% compared with 5% using guideline-based limits, a finding replicated in 908 participants in the CCHS. These findings suggest that relatively subtle impairments of systolic function (detected based on LVEF or strain) are independently associated with incident HF and HF with reduced LVEF in late life. Current recommended assessments of LV function may substantially underestimate the prevalence of prognostically important impairments in systolic function in this population.

Identification of Subclinical Myocardial Dysfunction in Breast Cancer Patients with Metabolic Syndrome after Cancer-Related Comprehensive Therapy.

Background Breast cancer patients with metabolic syndrome have an increased risk of cardiovascular disease. These patients are more prone to suffer from cardiotoxicity after anticancer therapy. Patients after completion of cancer-related comprehensive therapy, who show normal myocardial function, may already have subclinical myocardial dysfunction. We sought to evaluate the subclinical myocardial dysfunction in breast cancer patients with metabolic syndrome after cancer-related comprehensive therapy. Methods. In this study, 45 breast cancer patients with metabolic syndrome after completion of cancer-related comprehensive therapy, 45 non-breast cancer patients with metabolic syndrome, and 30 breast cancer patients without metabolic syndrome after therapy were enrolled. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured using echocardiogram. Results All the patients had normal LVEF. However, nine breast cancer patients with metabolic syndrome (20%) had GLS that was lower than –17%, while all the noncancer patients had normal GLS. Breast cancer patients with metabolic syndrome had a decrease of GLS and LVEF, compared with noncancer patients with metabolic syndrome. Furthermore, we found that decrease of age was associated with reduction of LVEF and that use of trastuzumab for 1 year was a significant factor associated with reduction of GLS. In addition, breast cancer patients with metabolic syndrome had a decrease of GLS, compared with breast cancer patients without metabolic syndrome after cancer-related therapy. Conclusions Breast cancer patients with metabolic syndrome after completion of cancer-related comprehensive therapy suffered from subclinical myocardial dysfunction. GLS should be routinely performed to early identify subclinical myocardial damage of patients, in order to prevent the cardiotoxicity of cancer-related comprehensive therapy.

Functional assessment in left ventricular non-compaction cardiomyopathy in multimodality imaging era might improve the definition

Abstract Left ventricular non-compaction (LVNC) is an increasingly recognized phenotype. The current definition of the LVNC does not mention LV dysfunction as an absolute criterion in addition to morphological criteria. LV dilatation and decreased LV ejection fraction (LVEF) are often late manifestations of the disease and correlate with the occurrence of cardiovascular complications. However, to define LVNC as a cardiomyopathy, functional criteria must be fulfilled, in addition to the morphological ones. Multimodality imaging, such as myocardial deformation and myocardial work analysis derived from speckle tracking echocardiography (STE), in combination with cardiac magnetic resonance (CMR) might improve diagnosis and characterization of non-compaction, exposing earlier signs of LV systolic dysfunction. We present two comparative cases of LVNC in order to highlight the idea of subclinical dysfunction even in apparently benign forms with preserved LVEF, and also the importance of multimodality imaging approach.