Phase III trial of non-pegylated liposomal doxorubicin (M) in combination with trastuzumab (T) and paclitaxel (P) in HER2+ metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 517-517 ◽  
Author(s):  
Lorena De La Pena ◽  
Javier Cortes ◽  
Alexey Manikhas ◽  
Laslo Roman ◽  
Vladimir Semiglazov ◽  
...  
Keyword(s):  
Nyha Class ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Ventricular Ejection Fraction ◽  
Phase Iii Trial

517 Background: M in combination with T has shown promising activity and cardiac safety in MBC patients (pts). We conducted a randomized Phase III trial of first-line M plus T and P (MTP) versus T plus P (TP) in HER2+ MBC pts. Methods: Pts with HER2+ (by FISH) MBC ≥ 18 years and ECOG 0-1, who had received no prior chemotherapy for metastatic disease, were eligible. Left ventricular ejection fraction should be within normal institutional limits. Prior (neo-) adjuvant anthracyclines, T or P were permitted, if completed >1 year before the start of the study. Pts received M 50 mg/m2 q3w for 6 cycles, T 4 mg/kg loading dose followed by 2 mg/kg qw, and P 80 mg/m2qw, or T+P at the same doses until progression or toxicity. Primary outcome was progression-free survival (PFS). Enrollment of 332 pts would provide 80% power with a 5% significance to detect an improvement in PFS with MTP, assuming a median PFS of 8 months in TP and a hazard ratio (HR) of 0.70. Results: 363 pts enrolled (MTP 181, TP 183), 360 received treatment. The two groups were well balanced for demographics, pretreatment characteristics and extent of disease. One third of the pts had prior exposure to anthracyclines, but almost none to trastuzumab (1% and 2% in MTP and TP arms, respectively). Six cycles of M could be given to 72% of the pts. With a median follow-up of 31 months, median PFS was 16.1 and 14.5 months with MTP and TP, respectively (HR 0.84, P=0.174). In pts with ER and PR-negative tumors, PFS was 20.7 and 14.0 months, respectively (HR, 0.68; 95% CI 0.47–0.99). Median overall survival (OS) was 33.6 and 28.9 months, respectively (HR, 0.79, P=0.083). In ER and PR-negative tumors, OS was 38.2 and 27.9 months, respectively (HR, 0.63; 95% CI 0.42–0.93). The incidence of NYHA Class III/IV congestive heart failure was 3% with MTP and there were 2 cardiac deaths with TP. The frequency of adverse events was higher with MTP, especially myelosuppression, stomatitis and gastrointestinal intolerance. Conclusions: The trial failed to demonstrate a significant clinical improvement with the addition of M to TP. The clinical benefit observed in an exploratory analysis in the ER and PR-negative population deserves consideration for further clinical trials. Clinical trial information: NCT00294996.

A phase I trial of pegylated liposomal anthracycline and lapatinib (L) combination in the treatment of metastatic breast cancer (MBC): First evaluation of an anthracycline and lapatinib combination in the treatment of MBC

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1079-1079 ◽  
Author(s):  
M. E. Cianfrocca ◽  
S. T. Rosen ◽  
J. H. von Roenn ◽  
A. W. Rademaker ◽  
S. D. Rubin ◽  
...  
Keyword(s):  
Phase I ◽  
Tyrosine Kinases ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Primary Objective ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Open Label ◽  
Ventricular Ejection Fraction

1079 Background: Liposomal formulations such as pegylated liposomal doxorubicin (PLD) were developed to improve the therapeutic index and overall benefit of the anthracyclines (A). L is a selective and highly competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases. The combination of conventional doxorubicin and an ErbB2 targeting agent (trastuzumab), while effective, led in a randomized phase III trial to an unacceptable risk of cardiac toxicity. The combination of PLD and L however may be effective with less cardiac risk Methods: This is an open-label, phase I, dose-escalation trial of PLD at 20, 30, 45 and 60 mg/m2 IV every 4 weeks (maximum of 8 doses) and L, 1,500 mg po daily until progression in patients (pts) with MBC. EGFR and/or ErbB2 positivity was not required. Prior chemotherapy, endocrine therapy and trastuzumab were allowed however prior A use was limited to 240 mg/m2 of doxorubicin or 600 mg/m2 of epirubicin and prior EGFR targeting therapies were not allowed. Concomitant CYP3A4 inducers/ inhibitors were not allowed. A left ventricular ejection fraction (LVEF) of ≥ 50% was required. The primary objective was to evaluate the safety, tolerability and feasibility of the combination of PLD and L, particularly with respect to cardiac safety. MUGAs were performed at entry and every 8 weeks thereafter. Results: 7 patients (PLD: 20 mg/m2 - 3 pts; 30 mg/m2 - 3 pts; and 45 mg/m2 - 1 pt) with a mean age of 43 yrs (range, 33–68) have been treated for a total of 14 treatment cycles. Dose-limiting toxicity (DLT) has not been reached. One pt experienced an LVEF drop to < 50% after 4 cycles however this was accompanied by a pericardial effusion felt to be secondary to progressive disease. Adverse events observed include: grade III/IV- none; grade I/II in ≥2 pts- rash, nausea, and anorexia; grade II leukopenia, fatigue, alopecia, diarrhea, headache were also seen in 1 pt each. Preliminary response data in 4 evaluable pts reveals 1 PR, 1 SD, and 2 PD. Conclusions: In the first 7 pts treated, the combination of PLD and L has been well tolerated. One pt experienced an LVEF drop to < 50%, however this was felt likely to be disease-related. DLT has not yet been reached and accrual is ongoing. No significant financial relationships to disclose.

scholarly journals Incidence of Cardiotoxicity and Validation of the Heart Failure Association- International Cardio-Oncology Society risk stratification Tool in Patients Treated with Trastuzumab for HER2-Positive Early Breast Cancer.

2021 ◽  
Author(s):  
Nicolò Matteo Luca Battisti ◽  
Maria Sol Andres ◽  
Karla A Lee ◽  
Tharshini Ramalingam ◽  
Tamsin Nash ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Early Breast Cancer ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Very High

Abstract PurposeTrastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates (left ventricular ejection fraction [LVEF] decline, congestive heart failure [CHF], cardiac death or trastuzumab discontinuation) and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.MethodsPatients receiving curative trastuzumab between 2011-2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, chi-squared and logistic regression were used.Results931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%).Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline≥10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed.Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p=0.002). ConclusionsCardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity

Safety analysis from PACS 04—A phase III trial comparing 6 cycles of FEC100 with 6 cycles of ET75 for node-positive early breast cancer patients, followed by sequential trastuzumab in HER2+ patients: Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 632-632 ◽  
Author(s):  
M. Spielmann ◽  
H. Roché ◽  
T. Delozier ◽  
G. Romieu ◽  
H. Bourgeois ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Safety Data ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Phase Iii Trial ◽  
Post Surgery

632 Background: Following the BCIRG 001, PACS 01 and HERA trials, this randomised, multicentre, open-label, Phase III trial was designed to demonstrate the benefit of concomitant docetaxel and epirubicin versus anthracyclines, and evaluate the use of sequential trastuzumab. Methods: Patients (pts) with localised, resectable, unilateral breast cancer who met the following criteria were eligible: age <65 years, ≥1 positive node, M0, adequate heart and organ functions. Pts were randomised to receive either 6 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (FEC100: F and C, 500 mg/m2, E 100 mg/m2) (Arm A) or epirubicin-docetaxel (ET75: E 75 mg/m2, T 75 mg/m2) (Arm B). Primary prophylaxis with G-CSF was not planned. Radiotherapy was mandatory after conservative surgery and tamoxifen was required in pts with hormone receptor-positive tumours. Pts with HER2-positive disease were then further randomised to observation only or to 1 year of trastuzumab monotherapy (6 mg/kg iv every 3 weeks). In HER2-positive pts receiving trastuzumab, left ventricular ejection fraction (LVEF) was determined at Cycles 2, 4, 8, 13, 18 and after 2 years. Otherwise, LVEF was determined at baseline and at 1 year post-surgery. Results: Of the 3010 pts recruited (2622 evaluable for safety to date), 1518 received FEC100 and 1492 received ET75 after the first randomisation. Haematologic toxicity was the most frequent toxicity in both arms. Grade 3–4 toxicities were similar for Arms A and B, except febrile neutropenia (10.3% and 31.4%, respectively) and nausea/vomiting (13.2% and 7.5%, respectively). Grade 2 clinical cardiac toxicity (decreased LVEF) was observed in 4 pts in Arm A and 5 in Arm B, with median LVEF scores of 63% in both arms at the end of chemotherapy. HER2-positive pts (n=500) were then randomised to either receive trastuzumab (n=259) or observation only (n=241). Conclusions: These preliminary safety data indicate that FEC100 and ET75 were both well tolerated, with acceptable cardiac safety values. The trial is ongoing and further analysis regarding the use of trastuzumab in this setting will be presented. [Table: see text]

Pegylated liposomal doxorubicin (PLD) with bevacizumab (B) in second-line treatment of ovarian cancer (OC): Pharmacokinetics (PK), safety, and preliminary outcome results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5548-5548
Author(s):  
F. M. Muggia ◽  
L. Boyd ◽  
L. Liebes ◽  
A. Downey ◽  
C. Muller ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Disease Status ◽  
Left Ventricular ◽  
Uncontrolled Hypertension ◽  
Left Ventricular Ejection ◽  
Parameter Estimates ◽  
Ventricular Ejection Fraction ◽  
Grade 3

5548 Background: PLD activity in platinum-resistant OC is modest. B, with its activity in platinum(Plat)-sensitive and Plat-resistant patients (pts), has not been combined with PLD. PLD intratumoral concentrations, if affected by B, might be reflected in PLD PK. This phase II study of PLD + B was started in 2007 to accrue 48 pts, unless 4 serious (> grade 3) adverse events (AEs) supervened. Methods: Improvement in progression-free survival (PFS) at 6 m from 25 to 40% at 6 m in Plat-resistant OC is primary endpoint. PK of PLD alone at 1h, d 7 and d 21 (cycle 1) vs with B (cycle 2), safety, and response rates (RECIST and CA125 criteria) were secondary endpoints. Dosing: PLD 30 mg/m2 followed by B 15 mg/kg on cycles 2–7 (with option to continue) d 1 every 3 w. Pts recurring within 6 m of platinum-based treatment for OC after < 3 prior regimens (but no PLD or B) were eligible. Exclusions: bowel obstruction, prior perforation, uncontrolled hypertension, or vascular disease. Hematologic, mucocutaneous and renal toxicities were evaluated prior to each cycle, MUGA scans every third cycle; disease status by CA125 and/or RECIST every third cycle. Results: 21 of 24 pts enrolled to date are evaluable. Median age is 65, range 52–83; most had 2 prior chemotherapy regimens. Median 6 (range 3–12) cycles were given with 6 off study with progression at 3–7 cycles. RECIST and CA125 responses are under review; in 11 pts with baseline CA125 of > 40 IU/mL, median increase was 31% by cycle 2; later falling to -57%. AEs did not exceed grade 3; hand-foot syndrome led to PLD dose reduction in 8 pts (33%); asymptomatic decreases in left ventricular ejection fraction (LVEF) >10% in 3 pts were noted, with treatment discontinuation in 1. The mean (±SEM) secondary PK parameter estimates for Cmax, AUC, and elimination half life were 4.5 ± 0.5 ug/mL, 651.7 ± 61 ug/mL x h, and 93.3 ± 19.7 h, respectively. Conclusions: Cycles 1 and 2 PLD PK do not differ. PLD + B is tolerable with PLD dose modifications. Declines in LVEF in 1 institution have uncertain causality. Midway into the trial, safety and time on study encourage completion for study primary endpoint. [Table: see text]

A phase III, randomized, double-blind, placebo (Pla)-controlled study of pertuzumab (P) + trastuzumab (H) + docetaxel (D) versus Pla + H+ D in previously untreated HER2-positive locally recurrent/metastatic breast cancer (LR/MBC) (PUFFIN).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1026-1026 ◽  
Author(s):  
Binghe Xu ◽  
Wei Li ◽  
Qingyuan Zhang ◽  
Shao Zhimin ◽  
Wang Xiao Jia ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Controlled Study ◽  
Her2 Positive ◽  
Double Blind ◽  
Ventricular Ejection Fraction

1026 Background: In CLEOPATRA (NCT00567190), adding P to H + D significantly improved progression-free and overall survival (PFS/OS) v Pla + H + D in patients (pts) with previously untreated HER2-positive LR/MBC. PUFFIN (NCT02896855) is a China bridging study; the objective being to assess consistency of efficacy with CLEOPATRA. Methods: Pts with previously untreated HER2-positive LR/MBC were randomized 1:1 to P + H + D or Pla + H + D, stratified by visceral v non-visceral disease and hormone receptor status. The primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate (ORR in pts with measurable baseline disease), OS, and safety. The target sample size (240) was determined based on the consistency threshold for PFS, defined as hazard ratio (HR) < 0.81, which maintains ≥ 50% of the risk reduction determined in CLEOPATRA (HR 0.62). Results: Two hundred forty-three pts were randomized. Baseline/disease characteristics and prior therapies were generally balanced between arms. For PFS, the HR was 0.69 (95% CI 0.49, 0.99) in the ITT population. No cases of heart failure or symptomatic left ventricular ejection fraction decline were reported. Efficacy/safety are shown in the table. Conclusions: PUFFIN met its primary endpoint. Overall, efficacy data were consistent with CLEOPATRA (ITT population and Asian subgroup). Safety was also consistent and in line with the known P safety profile, with no new or unexpected signals reported. PUFFIN adds to the totality of data with P in previously untreated HER2-positive LR/MBC, and supports the favorable benefit–risk profile of P in Chinese pts. Clinical trial information: NCT02896855. [Table: see text]

Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Final overall survival (OS) from the phase III HERITAGE Trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1021-1021 ◽  
Author(s):  
Cornelius F. Waller ◽  
Aleksei Manikhas ◽  
Eduardo J. Pennella ◽  
Igor Bondarenko ◽  
Guzel Mukhametshina ◽  
...  
Keyword(s):  
Safety Data ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Low Grade ◽  
Similar Distribution ◽  
Cardiac Events ◽  
Double Blind ◽  
Ventricular Ejection Fraction

1021 Background: The multicenter, double-blind, randomized, parallel-group, phase 3 Heritage trial (NCT02472964) evaluated efficacy and safety of trastuzumab-dkst (Ogivri), a trastuzumab biosimilar, vs trastuzumab, plus taxane as first-line therapy for patients with HER2+ metastatic breast cancer. Overall response at week (wk) 24 and progression-free survival (PFS) at wk 48 have been reported (Rugo et al, JAMA 2017; ASCO 2018). Methods: Eligible patients were randomized 1:1 to trastuzumab-dkst or trastuzumab, plus taxane. After 24 wks, patients with responding/stable disease continued monotherapy per randomization. Safety and OS during maintenance, cumulative through 36 months of follow-up from last patient on study, are described. Results: 500 patients were randomized; 343 received monotherapy after 24 wks (trastuzumab-dkst, n = 179; trastuzumab, n = 164). 128 patients discontinued monotherapy (trastuzumab-dkst, n = 63; trastuzumab, n = 65); mean time to discontinuation was 19 months in both groups. Treatment-emergent adverse events (TEAEs) during monotherapy were similar for trastuzumab-dkst (69%) and trastuzumab (73%); most were low grade and serious TEAE rates were 6% in both groups. Cumulative rates of TEAEs of special interest were similar for hypersensitivity, pulmonary, and cardiac events (trastuzumab-dkst, 23%, 16%, and 5%; trastuzumab, 24%, 13%, and 5%). Incidences of left ventricular ejection fraction (LVEF) < 50% ≥1 time postbaseline (trastuzumab-dkst, 5%; trastuzumab, 3%) and LVEF < 50% postbaseline and ≥10% reduction (trastuzumab-dkst, 4%; trastuzumab, 3%) were low. At 36 months, 169 patients had received further lines of therapy, with similar distribution of HER2 treatments, endocrine therapies, and chemotherapies. Final median PFS was 11.1 months in both groups. Median duration of response was 9.9 and 9.8 months and median OS was 35.0 and 30.2 months for trastuzumab-dkst and trastuzumab, respectively: unstratified hazard ratio, 0.9 (95% CI, 0.70-1.17). Conclusions: Long-term safety data with similar median OS compared with originator trastuzumab further support the safety and efficacy profile of trastuzumab-dkst. Clinical trial information: NCT02472964.

scholarly journals 85 Diuretics trajectories in dilated cardiomyopathy

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Vincenzo Nuzzi ◽  
Antonio Cannatà ◽  
Paolo Manca ◽  
Caterina Gregorio ◽  
Giulia Barbati ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Nyha Class ◽  
Diuretic Therapy ◽  
Left Ventricular ◽  
Equivalent Dose ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Ventricular Ejection Fraction ◽  
Kaplan Meier

Abstract Aims Diuretics in heart failure (HF) are commended to relieve symptoms at lowest dosage effective. Dilated cardiomyopathy (DCM) is a particular HF setting with several variables that may influence disease trajectory. We aimed to assess the long-term use of diuretics in DCM, the possibility of withdrawal and to explore the prognostic correlations. Methods and results All consecutive DCM patients enrolled from 1990 to 2018 were considered eligible. All the patients had available the information about the furosemide-equivalent dose at baseline and at follow-up evaluation within 24 months. Patients were categorized in stable (diuretic dose variation &lt;50%), increasers (diuretics dose increase ≥50% or initiation of diuretic therapy), and decreasers (diuretics dose decrease ≥50% or never prescribed diuretics in the 24-months observation period). The prognostic role of the diuretics trajectory group was assessed with Kaplan Meier analysis and with a time-dependent multivariable model. The outcome measure was a composite of all-cause death/heart transplantation/HF hospitalization (ACD/HTx/HFH). 908 patients were included [mean age 50 ± 16, 70% male sex, 24% NYHA class III or IV, mean left ventricular ejection fraction (LVEF) 31 ± 9%, 66% treated with diuretics at baseline]. The furosemide-equivalent dose at enrolment had a linear association with the risk of outcome. Compared to other groups, decreaser patients were younger, had less HF symptoms, higher LVEF and more dilated left atrium. Decreasers had a lower prescription rate of diuretics and less frequent indication to renin-angiotensin inhibitors and mineralocorticoid receptors antagonists. Over a median follow-up of 122 (62–195) months decreasers had the lowest incidence of outcome, followed by stable, while increasers had the worst outcome (P &lt; 0.001). After adjustment for other prognosticators, compared to stable patients, decreasers had a reduced risk of ACD/HTx/HFH [HR: 0.497 (95% CI: 0.337–0.731)] while increasers had the highest risk of adverse outcome [HR: 2.027 (95% CI: 1.254–3.276)]. Similarly, amongst patients taking diuretics at baseline, the diuretics withdrawal was in independent outcome predictor. The only multivariable predictors of diuretics withdrawal were younger age and lower furosemide-equivalent dose at enrolment. Conclusions In DCM patients the diuretics dose at baseline is a strong prognosticator. Diuretics dose reduction or its withdrawal provides a prognostic benefit on hard outcome. Diuretics tapering in selected patients should be considered in the short-term follow-up to improve DCM prognosis.

scholarly journals The central arterial stiffness parameters in decompensated versus compensated states of heart failure: a paired comparative cohort study

2022 ◽  
Vol 74 (1) ◽  
Author(s):  
Ahmed El Fol ◽  
Waleed Ammar ◽  
Yasser Sharaf ◽  
Ghada Youssef
Keyword(s):  
Heart Failure ◽  
Arterial Stiffness ◽  
Ejection Fraction ◽  
Pulse Wave ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction

Abstract Background Arterial stiffness is strongly linked to the pathogenesis of heart failure and the development of acute decompensation in patients with stable chronic heart failure. This study aimed to compare arterial stiffness indices in patients with heart failure with reduced ejection fraction (HFrEF) during the acute decompensated state, and three months later after hospital discharge during the compensated state. Results One hundred patients with acute decompensated HFrEF (NYHA class III and IV) and left ventricular ejection fraction ≤ 35% were included in the study. During the initial and follow-up visits, all patients underwent full medical history taking, clinical examination, transthoracic echocardiography, and non-invasive pulse wave analysis by the Mobil-O-Graph 24-h device for measurement of arterial stiffness. The mean age was 51.6 ± 6.1 years and 80% of the participants were males. There was a significant reduction of the central arterial stiffness indices in patients with HFrEF during the compensated state compared to the decompensated state. During the decompensated state, patients presented with NYHA FC IV (n = 64) showed higher AI (24.5 ± 10.0 vs. 16.8 ± 8.6, p < 0.001) and pulse wave velocity (9.2 ± 1.3 vs. 8.5 ± 1.2, p = 0.021) than patients with NYHA FC III, and despite the relatively smaller number of females, they showed higher stiffness indices than males. Conclusions Central arterial stiffness indices in patients with HFrEF were significantly lower in the compensated state than in the decompensated state. Patients with NYHA FC IV and female patients showed higher stiffness indices in their decompensated state of heart failure.

Characteristics of Children with Acute Rheumatic Carditis from a High-Incidence Region: Importance of Unexplained Worsening of Functional Class

Cardiology ◽  
2020 ◽  
Vol 145 (8) ◽  
pp. 522-528
Author(s):  
Rajiv Narang ◽  
Anita Saxena ◽  
Sivasubramanian Ramakrishnan ◽  
Saurabh K. Gupta ◽  
Rajnish Juneja ◽  
...  
Keyword(s):  
Nyha Class ◽  
Public Health Problem ◽  
Left Ventricular ◽  
Functional Class ◽  
Left Ventricular Ejection ◽  
First Episode ◽  
Major Public Health Problem ◽  
Class Iii ◽  
Rheumatic Carditis ◽  
Ventricular Ejection Fraction

Background: Acute rheumatic fever (ARF) and acute rheumatic carditis (ARC) continue to be a major public health problem in developing countries. Objective: To study the characteristics of children with ARC being treated at a tertiary centre. Methods and Results: We studied 126 children (mean age 10.4 ± 2.3 years, range 5–15 years, 60% males) diagnosed with ARC by treating cardiologists. Most had lower socio-economic status. Fifty of 126 (40%) presented with a first episode of ARC. Joint symptoms were present in 29% and fever in 25%. Only 2.4% had subcutaneous nodules and none had erythema marginatum or chorea. Fifty-one percent presented in NYHA class II and 29% in NYHA class III or IV. Tachycardia and heart failure were present in 53% and 21%, respectively. Recent worsening of NYHA class (dyspnoea) was the commonest feature (48%). Laboratory investigations showed raised antistreptolysin O titres (>333 units) in only 36.7% of patients. Raised C-reactive protein (CRP) was present in 70%, while raised erythrocyte sedimentation rate was found in only 37% of patients. On the basis of above findings, the modified Jones criteria (2015) for the diagnosis of ARF were satisfied only in 46% of children. Echocardiography showed mitral valve thickening in 77% and small nodules on the tip of the leaflets in 43% (27 and 8%, respectively for aortic valve). Left ventricular ejection fraction was <50% in only 3 patients. The dominant valve lesion was mitral regurgitation (MR) (present in 95% of patients; severe in 78%, moderate in 15%), while aortic regurgitation was present in 44% (severe in 14%). Conclusions: The criteria are often not satisfied by patients being treated for ARC. Recent unexplained worsening of dyspnoea, young age, significant MR, echocardiographic nodules, and elevated CRP are important indicators.

Long-term outcomes and left ventricular diastolic function of sarcomere mutation-positive and mutation-negative patients with hypertrophic cardiomyopathy: a prospective cohort study

2020 ◽  
Author(s):  
Ching-Yu Julius Chen ◽  
Mao-Yuan Marine Su ◽  
Ying-Chieh Liao ◽  
Fu-Lan Chang ◽  
Cho-Kai Wu ◽  
...  
Keyword(s):  
New York ◽  
Hypertrophic Cardiomyopathy ◽  
Nyha Class ◽  
Global Longitudinal Strain ◽  
Heart Association ◽  
Left Ventricular Diastolic Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Ventricular Ejection Fraction

Abstract Aims Hypertrophic cardiomyopathy (HCM) is an inheritable disease that leads to sudden cardiac death and heart failure (HF). Sarcomere mutations (SMs) have been associated with HF. However, the differences in ventricular function between SM-positive and SM-negative HCM patients are poorly characterized. Methods and results  Of the prospectively enrolled 374 unrelated HCM patients in Taiwan, 115 patients underwent both 91 cardiomyopathy-related gene screening and cardiovascular magnetic resonance (45.6 ± 10.6 years old, 76.5% were male). Forty pathogenic/likely pathogenic mutations were identified in 52 patients by next-generation sequencing. The SM-positive group were younger at first cardiovascular event (P = 0.04) and progression to diastolic HF (P = 0.02) with higher N-terminal pro-brain natriuretic peptide (NT-proBNP) [New York Heart Association (NYHA) Class III/IV symptoms with left ventricular ejection fraction &gt; 55%] than the SM-negative group (P &lt; 0.001). SM-positive patients had a greater extent of late gadolinium enhancement (P = 0.01), larger left atrial diameter (P = 0.03), higher normalized peak filling rate (PFR) and PFR ratio, and a greater reduction in global longitudinal strain than SM-negative patients (all P ≤ 0.01). During mean lifelong follow-up time (49.2 ± 15.6 years), SM-positive was a predictor of earlier HF (NYHA Class III/IV symptoms) after multivariate adjustment (hazard ratio 3.5; 95% confidence interval 1.3–9.7; P = 0.015). Conclusion SM-positive HCM patients had a higher extent of myocardial fibrosis and more severe ventricular diastolic dysfunction than those without, which may contribute to earlier onset of advanced HF, suggesting the importance of close surveillance and early treatment throughout life.

Sign in / Sign up

Export Citation Format

Share Document