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JACC. Clinical Electrophysiology Sep 2023The anatomical substrate for left posterior fascicular ventricular tachycardia (LPF-VT) is still unclear.
BACKGROUND
The anatomical substrate for left posterior fascicular ventricular tachycardia (LPF-VT) is still unclear.
OBJECTIVES
The purpose of this study is to describe the endocavitary substrate of the re-entrant loop of LPF-VT.
METHODS
A total of 26 consecutive patients with LPF-VT underwent an electrophysiology study and radiofrequency ablation.
RESULTS
Intracardiac echocardiography imaging observed a 100% prevalence of false tendons (FTs) at the left posterior septal region in all patients, and 3 different types of FTs could be classified according to their location. In 22 patients, a P1 potential could be recorded via the multielectrode catheter from a FT. In 4 patients without a recorded P1 during LPF-VT, the earliest P2 potentials were recorded from a FT in 3 patients, and from a muscular connection between 2 posteromedial papillary muscles in 1 patient. Catheter ablation focused on the FTs with P1 or earliest P2 (in patients without P1) was successful in all 26 patients. After 19 ± 8.5 months of follow-up, no patients had recurrence of LPF-VT.
CONCLUSIONS
FTs provide an electroanatomical substrate for LPF-VT and a "culprit FT" may be identified as the critical structure bridging the macro-re-entrant loop. Targeting the "culprit FT" is a novel anatomical ablation strategy that results in long-term arrhythmia-free survival.
Topics: Humans; Heart Ventricles; Electrocardiography; Bundle-Branch Block; Tachycardia, Ventricular; Electrophysiologic Techniques, Cardiac; Catheter Ablation
PubMed: 37480871
DOI: 10.1016/j.jacep.2023.05.036 -
Journal of Cardiothoracic Surgery Mar 2024Ischaemic secondary mitral regurgitation (ISMR) after surgery is due to the displacement of papillary muscles resulting from progressive enlargement of the left... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Ischaemic secondary mitral regurgitation (ISMR) after surgery is due to the displacement of papillary muscles resulting from progressive enlargement of the left ventricle end-diastolic diameter (LVEDD). Our aim was to prove that if the interpapillary muscle distance (IPMD) is surgically stabilized, an increase in LVEDD will not lead to a recurrence of ischaemic mitral regurgitation (MR).
METHODS
Ninety-six patients with ISMR, who underwent surgical revascularisation and annuloplasty, were randomly assigned in a 1:1 ratio to undergo papillary muscle approximation (PMA). At the 5-year follow-up, we assessed the correlation between PMA and echocardiographic improvements, the effect size of PMA on echocardiographic improvements, and a prediction model for recurrent MR using inferential tree analysis.
RESULTS
There was a significant correlation between PMA and enhancements in both the α and β angles (Spearman's rho > 0.7, p < 0.01). The α angle represents the angle between the annular plane and either the A2 annular-coaptation line or the P2 annular-coaptation line. The β angle indicates the angle between the annular plane and either the A2 annular-leaflet tip line or the P2 annular-leaflet tip line. PMA led to substantial improvements in LVEDD, tenting area, α and β angles, with a large effect size (Hedge's g ≥ 8, 95% CI ORs ≠ 1). The most reliable predictor of recurrent MR grade was the interpapillary distance, as only patients with an interpapillary distance greater than 40 mm developed ≥ 3 + grade MR. For patients with an IPMD of 40 mm or less, the best predictor of recurrent MR grade was LVEDD. Among the patients, only those with LVEDD greater than 62 mm showed moderate (2+) MR, while only those with LVEDD less than or equal to 62 mm had absent to mild (1+) MR.
CONCLUSION
Prediction of recurrent ischaemic MR is not independent of progressive LVEDD increase. PMA-based surgical procedure stabilises IPMD.
Topics: Humans; Mitral Valve Insufficiency; Mitral Valve; Echocardiography; Papillary Muscles; Heart Ventricles; Mitral Valve Annuloplasty
PubMed: 38509555
DOI: 10.1186/s13019-024-02631-z -
International Journal of Molecular... Aug 2023Aerobic exercise training (AET) has been used to manage heart disease. AET may totally or partially restore the activity and/or expression of proteins that regulate...
Aerobic exercise training (AET) has been used to manage heart disease. AET may totally or partially restore the activity and/or expression of proteins that regulate calcium (Ca) handling, optimize intracellular Ca flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca transit and cardiac function in rats with heart failure resulting from aortic stenosis (AoS). This study aimed to evaluate the impact of AET on Ca handling and cardiac function in rats with heart failure due to AoS. Wistar rats were distributed into two groups: control (Sham; = 61) and aortic stenosis (AoS; = 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, = 28 and AoS, = 22) and trained (Sham-ET, = 33 and AoS-ET, = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. The cardiac function was analyzed by echocardiogram, isolated papillary muscles, and isolated cardiomyocytes. During assays of isolated papillary muscles and isolated cardiomyocytes, the Ca concentrations were evaluated. The expression of regulatory proteins for diastolic Ca was assessed via Western Blot. AET attenuated the diastolic dysfunction and improved the systolic function. AoS-ET animals presented an enhanced response to post-rest contraction and SERCA2a and L-type Ca channel blockage compared to the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca of the AoS-ET animals. AoS animals presented an alteration in the protein expression of SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity and myofilament responsiveness to Ca and improved the cellular Ca influx mechanism, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with AoS and heart failure.
Topics: Rats; Animals; Calcium; Rats, Wistar; Heart Failure; Myocytes, Cardiac; Calcium, Dietary; Aortic Valve Stenosis; Exercise; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 37569680
DOI: 10.3390/ijms241512306 -
World Journal of Cardiology May 2024Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral regurgitation. Achieving precise measurements of...
BACKGROUND
Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral regurgitation. Achieving precise measurements of artificial chordae tendineae length (CL) is an important factor in the procedure; however, no objective index currently exists to facilitate this measurement. Therefore, preoperative assessment of CL is critical for surgical planning and support. Four-dimensional x-ray micro-computed tomography (4D-CT) may be useful for accurate CL measurement considering that it allows for dynamic three-dimensional (3D) evaluation compared to that with transthoracic echocardiography, a conventional inspection method.
AIM
To investigate the behavior and length of mitral chordae tendineae during systole using 4D-CT.
METHODS
Eleven adults aged > 70 years without mitral valve disease were evaluated. A 64-slice CT scanner was used to capture 20 phases in the cardiac cycle in electrocardiographic synchronization. The length of the primary chordae tendineae was measured from early systole to early diastole using the 3D image. The primary chordae tendineae originating from the anterior papillary muscle and attached to the A1-2 region and those from the posterior papillary muscle and attached to the A2-3 region were designated as cA and cP, respectively. The behavior and maximum lengths [cA (ma), cP (max)] were compared, and the correlation with body surface area (BSA) was evaluated.
RESULTS
In all cases, the mitral anterior leaflet chordae tendineae could be measured. In most cases, the cA and cP chordae tendineae could be measured visually. The mean cA (max) and cP (max) were 20.2 mm ± 1.95 mm and 23.5 mm ± 4.06 mm, respectively. cP (max) was significantly longer. The correlation coefficients (r) with BSA were 0.60 and 0.78 for cA (max) and cP (max), respectively. Both cA and cP exhibited constant variation in CL during systole, with a maximum 1.16-fold increase in cA and a 1.23-fold increase in cP from early to mid-systole. For cP, CL reached a plateau at 15% and remained elongated until end-systole, whereas for cA, after peaking at 15%, CL shortened slightly and then moved toward its peak again as end-systole approached.
CONCLUSION
The study suggests that 4D-CT is a valuable tool for accurate measurement of both the length and behavior of chordae tendineae within the anterior leaflet of the mitral valve.
PubMed: 38817650
DOI: 10.4330/wjc.v16.i5.274 -
Kardiologiia Aug 2023The article describes a clinical case of cardiac rhabdomyoma first diagnosed in an 18-year-old girl. At the age of 12 months, the patient first developed generalized,...
The article describes a clinical case of cardiac rhabdomyoma first diagnosed in an 18-year-old girl. At the age of 12 months, the patient first developed generalized, prolonged convulsive seizure with the eyeballs rolling upward, tonic arm tension, and profuse salivation. From 1.5 to 2 years, according to her mother, the girl had frequent "freezing" with fixed stare. Anticonvulsant therapy was not administered. From the age of 2 years 8 months, the child began to experience episodes of drowsiness, lethargy, blurred speech, and repeated vomiting lasting up to 2 weeks. The patient was regularly treated at the neurological department. According to CT at the age of four, the patient showed characteristic alterations in the brain and was diagnosed with tuberous sclerosis, symptomatic generalized epilepsy, and psychoorganic syndrome. Only at the age of 18, cardiac ultrasound detected a 7x6 mm hyperechoic formation with endogenous growth buried in the myocardium of the left ventricular (LV) anterior-lateral wall and another one in the area of the LV lateral wall with endogenous growth of 2×4 mm. Magnetic resonance imaging (MRI) revealed multiple focal formations with clear, even contours in the area of the middle anterior septal segment (closely adjacent to papillary muscles) in the region of the apex, buried in the myocardium. The formation sizes were 9×7 mm, 8×13 mm, and 7.5×6 mm, respectively, and they moderately accumulated the contrast agent. Lesions with identical characteristics and a diameter up to 4.5 mm were visualized on the anterior wall in the region of the apex, in the depth of the myocardium. Due to the absence of arrhythmias and hemodynamic disorders, immunosuppressive therapy was not administered. Follow-up and dynamic MRI control of the heart were recommended. If signs of tumor growth are detected, consider immunosuppressive therapy with everolimus. The case is of interest for a long asymptomatic growth of rhabdomyoma. Generally, cardiac rhabdomyomas are diagnosed in the postnatal period and may be the earliest manifestation of tuberous sclerosis.
Topics: Humans; Child; Female; Infant; Child, Preschool; Adolescent; Rhabdomyoma; Tuberous Sclerosis; Heart; Myocardium; Heart Ventricles; Heart Neoplasms
PubMed: 37691508
DOI: 10.18087/cardio.2023.8.n1821 -
Frontiers in Cardiovascular Medicine 2023Anomalous papillary muscle (APM) insertion into the mitral valve leaflet is rare but clinically important in hypertrophic obstructive cardiomyopathy (HOCM). In this...
BACKGROUND
Anomalous papillary muscle (APM) insertion into the mitral valve leaflet is rare but clinically important in hypertrophic obstructive cardiomyopathy (HOCM). In this study, we report the detection rate of APM insertion into the mitral valve using preoperative imaging modalities and the surgical outcomes of the patients.
METHODS
By retrospectively reviewing the clinical records of patients with HOCM who underwent surgical treatment by a single operation group at our center from January 2020 to June 2023, patients with APM insertion into the mitral valve leaflet were identified. Baseline data, image characteristics, and surgical outcomes were analyzed.
RESULTS
The incidence of APM insertion into the mitral valve leaflet was 5.1% (8/157). The insertion site was located at A3 in six cases, which was more common than at A2 (=2). Preoperative echocardiography was used to identify two patients (25%) with APM insertion. We observed a particular echocardiographic feature for APM in HOCM patients, which was noted as a "lip nevus sign", with a higher detection rate (62.5%). All patients successfully underwent septal myectomy with concomitant APM excision or mitral valve replacement via the transaortic (=5) or transmitral (=3) approach. The mean age was 49.0 ± 17.4 years and seven patients (87.5%) were female. Interventricular septum thickness (17.0 mm vs. 13.3 mm, =0.012) and left ventricular outflow gradient (117.5 mmHg vs. 7.5 mmHg, =0.012) were significantly decreased after surgery. Residual outflow obstruction, systolic anterior motion, and ≥3+ mitral regurgitation were negative. During the follow-up of 26.2 ± 12.2 months, there were no reported operations, adverse events, mitral regurgitation aggravations, recurrences of outflow obstruction, or instances of SAM.
CONCLUSIONS
Papillary muscles inserted into the mitral valve leaflet are a subtype of subvalvular malformation in HOCM that requires surgical correction. The lip nevus sign on echocardiography is a characteristic of APM insertion in HOCM and may improve the preoperative detection rate. Adequate myectomy with anomalous papillary muscle excision has achieved good results in reducing the outflow gradient and eliminating mitral regurgitation, with good outcomes at short-to-intermediate follow-up.
PubMed: 38124897
DOI: 10.3389/fcvm.2023.1292142 -
The Lancet. Oncology Jun 2024The KEYNOTE-057 trial evaluated activity and safety of pembrolizumab in patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer who were ineligible...
Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): a single-arm, multicentre, phase 2 trial.
BACKGROUND
The KEYNOTE-057 trial evaluated activity and safety of pembrolizumab in patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer who were ineligible for or declined radical cystectomy. In cohort A (patients with carcinoma in situ, with or without papillary tumours) of the KEYNOTE-057 study, pembrolizumab monotherapy led to a complete response rate of 41% at 3 months, and 46% of responders maintained a response lasting at least 12 months. Here, we evaluate pembrolizumab monotherapy in cohort B of patients with papillary tumours without carcinoma in situ.
METHODS
KEYNOTE-057 is a single-arm, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. Cohort B eligible patients were aged 18 years and older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had BCG-unresponsive high-risk non-muscle-invasive bladder cancer with papillary tumours (high-grade Ta or any-grade T1) without carcinoma in situ. Transurethral resection of bladder tumour within 12 weeks of first pembrolizumab dose was required. Patients received pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles. Primary endpoint was 12-month disease-free survival of high-risk non-muscle-invasive bladder cancer or progressive disease as assessed by cystoscopy, cytology, and central pathology and radiology review. Activity was assessed in all patients who received at least one dose of the study drug and had a baseline evaluation. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961, and is ongoing.
FINDINGS
Between April 12, 2016, and June 17, 2021, 132 patients (104 [79%] men and 28 [21%] women) who had received a median of ten (IQR 9-15) previous BCG instillations were enrolled into cohort B of the study. Patients received a median of 10 cycles (IQR 6-27) of pembrolizumab. At data cutoff date, Oct 20, 2022, median follow-up was 45·4 months (IQR 36·4-59·3) and five (4%) of 132 patients remained on treatment. The 12-month disease-free survival was 43·5% (95% CI 34·9-51·9). Treatment-related adverse events occurred in 97 (73%) of 132 patients; 19 (14%) had a grade 3 or 4 treatment-related adverse event; the most common grade 3 or 4 treatment-related adverse events were colitis (in three [2%] patients) and diarrhoea (in two [2%]). 17 (13%) of 132 patients experienced serious treatment-related adverse events, of which colitis (three patients [2%]) was most common. No treatment-related deaths occurred.
INTERPRETATION
Pembrolizumab monotherapy showed antitumour activity and manageable toxicity in patients with BCG-unresponsive high-risk Ta or T1 bladder cancer without carcinoma in situ and could potentially be a suitable treatment option for patients who decline or are ineligible for radical cystectomy. Findings will need to be confirmed in a randomised controlled trial.
FUNDING
Merck Sharp & Dohme.
Topics: Humans; Urinary Bladder Neoplasms; Antibodies, Monoclonal, Humanized; Male; Female; Aged; BCG Vaccine; Middle Aged; Antineoplastic Agents, Immunological; Carcinoma in Situ; Neoplasm Invasiveness; Aged, 80 and over; Non-Muscle Invasive Bladder Neoplasms
PubMed: 38740030
DOI: 10.1016/S1470-2045(24)00178-5 -
Journal of the American College of... May 2024Severe acute mitral regurgitation after myocardial infarction includes partial and complete papillary muscle rupture or functional mitral regurgitation. Although its... (Review)
Review
Severe acute mitral regurgitation after myocardial infarction includes partial and complete papillary muscle rupture or functional mitral regurgitation. Although its incidence is <1%, mitral regurgitation after acute myocardial infarction frequently causes hemodynamic instability, pulmonary edema, and cardiogenic shock. Medical management has the worst prognosis, and mortality has not changed in decades. Surgery represents the gold standard, but it is associated with high rates of morbidity and mortality. Recently, transcatheter interventions have opened a new door for management that may improve survival. Mechanical circulatory support restores vital organ perfusion and offers the opportunity for a steadier surgical repair. This review focuses on the diagnosis and the interventional management, both surgical and transcatheter, with a glance on future perspectives to enhance patient management and eventually decrease mortality.
Topics: Humans; Mitral Valve Insufficiency; Myocardial Infarction; Severity of Illness Index; Cardiac Catheterization; Disease Management
PubMed: 38692830
DOI: 10.1016/j.jacc.2023.09.840 -
The International Journal of... Feb 2024Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This...
PURPOSE
Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies.
METHODS
MVP patients with indication for surgery due to severe mitral regurgitation (n = 19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE). CMR T1 mapping was performed on 21 healthy volunteers as controls. LV inferobasal myocardial biopsies were obtained in MVP patients and compared to CMR findings.
RESULTS
MVP patients (54 ± 10 years old, 14 male) had a dark-appearance of the PM with higher native T1 and extracellular volume (ECV) values compared with healthy volunteers (1096 ± 78ms vs. 994 ± 54ms and 33.9 ± 5.6% vs. 25.9 ± 3.1%, respectively, p < 0.001). Seventeen MVP patients (89.5%) had fibrosis by biopsy. BB-LGE + in LV and PM was identified in 5 (26.3%) patients, while DB-LGE + was observed in LV in 9 (47.4%) and in PM in 15 (78.9%) patients. DB-LGE + in PM was the only technique that showed no difference with detection of LV fibrosis by biopsy. Posteromedial PM was more frequently affected than the anterolateral (73.7% vs. 36.8%, p = 0.039) and correlated with biopsy-proven LV fibrosis (Rho 0.529, p = 0.029).
CONCLUSIONS
CMR imaging in MVP patients referred for surgery shows a dark-appearance of the PM with higher T1 and ECV values compared with healthy volunteers. The presence of a positive DB-LGE at the posteromedial PM by CMR may serve as a better predictor of biopsy-proven LV inferobasal fibrosis than conventional CMR techniques.
Topics: Humans; Male; Adult; Middle Aged; Mitral Valve Prolapse; Papillary Muscles; Heart Ventricles; Contrast Media; Predictive Value of Tests; Gadolinium; Fibrosis; Magnetic Resonance Imaging, Cine
PubMed: 37891450
DOI: 10.1007/s10554-023-02985-w -
European Urology Oncology Jun 2024Therapeutic options for patients with non-muscle-invasive bladder cancer (NMIBC) have traditionally been limited to intravesical immunotherapy or chemotherapy. A... (Review)
Review
BACKGROUND AND OBJECTIVE
Therapeutic options for patients with non-muscle-invasive bladder cancer (NMIBC) have traditionally been limited to intravesical immunotherapy or chemotherapy. A considerable number of new options have been investigated in recent years. Our aim was to review the efficacy and toxicity of novel therapeutic options (results already reported or currently under investigation) for patients with NMIBC.
METHODS
We assessed the efficacy of various novel therapeutic options by examining key endpoints in diverse settings, including recurrence, progression, overall survival, disease-specific survival, and complete response. We identified the principal advantages and limitations for each option. Safety was predominantly evaluated as the incidence of grade ≥3 adverse events. Our investigation focused on evidence from scientific articles and congress abstracts published in English within the past 5 yr.
KEY FINDINGS AND LIMITATIONS
To date, pembrolizumab, nadofaragene firadenovec, and the combination of BCG with N-803 have received US Food and Drug administration approval for the treatment of BCG-unresponsive carcinoma in situ of the bladder (with or without papillary tumours). Five phase 3 trials are recruiting BCG-naïve patients with high-risk NMIBC. There is increasing interest in an ablative rather than an adjuvant approach for patients with intermediate-risk NMIBC.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Novel drugs and device-assisted drug delivery systems are on the verge of changing the treatment of NMIBC. Novel intravesical options seem to have the same efficacy with fewer adverse events in comparison to systemic therapies.
PATIENT SUMMARY
We reviewed new therapy options for non-muscle-invasive bladder cancer. Two agents (pembrolizumab and nadofaragene firadenovec) have been approved to date. Ongoing trials are assessing direct delivery of drugs in solution into the bladder. This route seems to have similar efficacy and fewer side effects than intravenous immunotherapy.
PubMed: 38849286
DOI: 10.1016/j.euo.2024.05.012