Exploring Changes in Myocyte Structure, Contractility, and Energetics From Mechanical Unloading in Patients With Heart Failure Undergoing Ventricular Assist Device Implantation: A Systematic Review and Meta-Analysis.

AIMS: Recent reports of myocardial recovery after mechanical unloading with left ventricular assist devices (LVADs) have challenged the prevailing notion that end-stage heart failure (HF) is irreversible. To improve our understanding of this phenomenon, we comprehensively analysed the structural, functional, and energetic changes in failing human cardiomyocytes after LVAD implantation. METHODS: Based on a prospectively registered protocol (PROSPERO-CRD42022380214), 30 eligible studies were identified from 940 records with a pooled population of 648 patients predominantly with non-ischaemic cardiomyopathy. RESULTS: LVAD led to a substantial regression in myocyte size similar to that of donor hearts (standardised mean difference, -1.29; p<0.001). The meta-regression analysis revealed that HF duration was a significant modifier on the changes in myocyte size. There were some suggestions of fibrosis reversal (-5.17%; p=0.009); however, this was insignificant after sensitivity analysis. Developed force did not improve in cardiac trabeculae (n=5 studies); however, non-physiological isometric contractions were tested. At the myocyte level (n=4 studies), contractile kinetics improved where the time-to-peak force reduced by 41.7%-50.7% and time to 50% relaxation fell by 47.4%-62.1% (p<0.05). Qualitatively, LVAD enhanced substrate utilisation and mitochondrial function (n=6 studies). Most studies were at a high risk of bias. CONCLUSION: The regression of maladaptive hypertrophy, partial fibrosis reversal, and normalisation in metabolic pathways after LVAD may be a testament to the heart's remarkable plasticity, even in the advanced stages of HF. However, inconsistencies exist in force-generating capabilities. Using more physiological force-length work-loop assays, addressing the high risks of bias and clinical heterogeneity are crucial to better understand the phenomenon of reverse remodelling.

The Role of the Vasculature in Heart Failure.

The contribution of the vasculature in the development and progression of heart failure (HF) syndromes is poorly understood and often neglected. Incorporating both arterial and venous systems, the vasculature plays a significant role in the regulation of blood flow throughout the body in meeting its metabolic requirements. A deterioration or imbalance between the cardiac and vascular interaction can precipitate acute decompensated HF in both preserved and reduced ejection fraction phenotypes. This is characterised by the increasingly recognised concept of ventricular-arterial coupling: a well-balanced relationship between ventricular and vascular stiffness, which has major implications in HF. Often, the cause of decompensation is unknown, with international guidelines mainly centred on arrhythmia, infection, acute coronary syndrome and its mechanical complications as common causes of decompensation; the vascular component is often underrecognised. A better understanding of the vascular contribution in cardiovascular failure can improve risk stratification, earlier diagnosis and facilitate earlier optimal treatment. This review focuses on the role of the vasculature by integrating the concepts of ventricular-arterial coupling, arterial stiffness and venous return in a failing heart.

Initial experience of temperature-controlled irrigated radiofrequency ablation for ischaemic cardiomyopathy ventricular tachycardia ablation.

BACKGROUND: The DiamondTemp ablation (DTA) catheter system delivers high power, open-irrigated, temperature-controlled radiofrequency (RF) ablation. This novel ablation system has not been previously used for ventricular tachycardia (VT) ablation. OBJECTIVE: Feasibility of using the DTA catheter system for VT ablation in ischaemic cardiomyopathy (ICM) patients. METHOD: Ten ICM patients with optimal anti-arrhythmic drug therapy and implantable cardiac defibrillators (ICD) were recruited. VT inducibility testing was performed at the end of the procedure. ICD data for device detected VT episodes and device treated VT episodes were collected for 6-months pre- and post-ablation. RESULTS: Substrate analysis demonstrated reductions in the borderzone area of 4.4 cm2 (p = 0.026) and late potential area of 3.5 cm2 (p = 0.0449) post-ablation, with reductions in the mean bipolar and unipolar voltages of the ablation target areas (0.14 mV (p = 0.0007); 0.59 mV (p = 0.0072) respectively). Complete procedural success was achieved in 9 procedures. Post-ablation VT inducibility testing was not performed in 1 procedure due to a steam pop complication resulting in pericardial tamponade requiring drainage. Mean follow-up of 214 ± 33 days revealed an 88% reduction in total VT episodes (n = 266 median 16 [IQR 3-57] to n = 33 median 0; p = 0.0164) and 77% reduction in ICD therapies (n = 128 median 5 [IQR 2-15] to n = 30 median 0; p = 0.0181). CONCLUSION: The DTA system resulted in adequate lesion characteristics with effective substrate modification, acute procedural success and improved outcomes at intermediate-term follow-up. Randomised controlled trials are required to compare the performance of the DTA system against conventional ablation catheters.

Developing a contemporary community clinic for patients with heart failure with preserved ejection fraction within the current National Health Service model.

INTRODUCTION: The diagnostic and therapeutic arsenal for heart failure with preserved ejection (HFpEF) has expanded. With novel therapies (eg, sodium-glucose co-transporter 2 inhibitors) and firmer recommendations to optimise non-cardiac comorbidities, it is unclear if outpatient HFpEF models can adequately deliver this. We; therefore, evaluated the efficacy of an existing dedicated HFpEF clinic to find innovative ways to design a more comprehensive model tailored to the modern era of HFpEF. METHODS: A single-centre retrospective analysis of 202 HFpEF outpatients was performed over 12 months before the COVID-19 pandemic. Baseline characteristics, clinic activities (eg, medication changes, lifestyle modifications, management of comorbidities) and follow-up arrangements were compared between a HFpEF and general cardiology clinic to assess their impact on mortality and morbidity at 6 and 12 months. RESULTS: Between the two clinic groups, the sample population was evenly matched with a typical HFpEF profile (mean age 79±9.6 years, 55% female and a high prevalence of cardiometabolic comorbidities). While follow-up practices were similar, the HFpEF clinic delivered significantly more interventions on lifestyle changes, blood pressure and heart rate control (p<0.0001) compared with the general clinic. Despite this, no significant differences in all-cause hospitalisation and mortality were observed. This may be attributed to the fact that clinic activities were primarily cardiology-focused. Importantly, non-cardiovascular admissions accounted for >60% of hospitalisation, including causes of recurrent admissions. CONCLUSION: This study suggests that existing general and emerging dedicated HFpEF clinics may not be adequate in addressing the multifaceted aspects of HFpEF as clinic activities concentrated primarily on cardiological measures. Although the small cohort and short follow-up period are important limitations, this study reminds clinicians that HFpEF patients are more at risk of non-cardiac than HF-related events. We have therefore proposed a pragmatic framework that can comprehensively deliver the modern guideline-directed recommendations and management of non-cardiac comorbidities through a multidisciplinary approach.

Safety and outcome of nurse-led syncope clinics and implantable loop recorder implants.

BACKGROUND: Implantable loop recorders (ILRs) are effective in achieving symptom-rhythm correlation. Data on the diagnostic yield of ILRs, on nurse-led syncope clinics, and on nurse-led ILR implants are limited. OBJECTIVE: We evaluated the safety and efficacy of our nurse-led syncope clinic and nurse-led ILR implants. METHODS: A retrospective study of all consecutive patients undergoing nurse-led ILR implantations was performed between April 2016 and April 2018. Patients were referred from both nurse-led and physician-led clinics. Data were collected on baseline demographic characteristics, referral source, symptom-rhythm correlation, ILR findings, and subsequent changes to management. All ILRs were enrolled into remote monitoring with automatic arrhythmia detection, and all immediate (≤24 hours) ILR implant complications were recorded. Comparisons were made between nurse-led and physician-led clinics and subsequent outcomes. RESULTS: A total of 432 patients with an ILR were identified: 164 (38%) from nurse-led and 268 (62%) from physician-led clinics; 200 (46%) were women (mean age 66.5 ± 18.2 years; mean follow-up duration 28.9 ± 9.5 months). Primary ILR indications were syncope (n = 251 [58%]), presyncope (n = 33 [7%]), palpitation (n = 39 [9%]), cryptogenic stroke (n = 78 [18%]), and other reasons (n = 31 [7%]). No immediate ILR implant complications occurred. Overall, 156 patients (36%) had a change in management as a direct result of ILR findings, with no overall differences between nurse-led and physician-led clinics (35% vs 36%; P = .7). More patients had newly diagnosed atrial fibrillation in physician-led clinics (15% vs 7%; P = .01), and more patients had pacemaker implants for bradycardia in nurse-led clinics (23% vs 13%; P < .01). CONCLUSION: Nurse-led ILR implantation was safe and effective. Nurse-led syncope clinics achieved good symptom-rhythm correlation with resultant significant changes to management in comparison to physician-led clinics. Larger prospective studies are needed to evaluate their longer-term impact.

Safety and feasibility of trans-venous cardiac device extraction using conscious sedation alone-Implications for the post-COVID-19 era.

BACKGROUND: Transvenous lead extraction (TLE) for implantable cardiac-devices is traditionally performed under general anesthesia (GA). This can lead to greater risk of exposure to COVID-19, longer recovery-times and increased procedural-costs. We report the feasibility/safety of TLE using conscious-sedation alone with immediate GA/cardiac-surgery back-up if needed. METHODS: Retrospective case-series of consecutive TLEs performed using conscious-sedation alone between March 2016 and December 2019. All were performed in the electrophysiology-laboratory using intravenous Fentanyl, Midazolam/Diazepam with a stepwise approach using locking-stylets/cutting-sheaths, including mechanical-sheaths. Baseline patient-characteristics, procedural-details and TLE outcomes (including procedure-related complications/death) were recorded. RESULTS: A total of 130 leads were targeted in 54 patients, mean age ± SD 74.6 ± 11.8years, 47(87%) males; dual-chamber pacemakers (n = 26; 48%), cardiac resynchronization therapy-defibrillators (n = 17; 31%) and defibrillators (n = 8; 15%) were commonest extracted devices. Mean ± SD/median (range) lead-dwell times were 11.0 ± 8.8/8.3 (0.3-37) years, respectively. Extraction indications included systemic infection (n = 23; 43%) and lead/pulse-generator erosion (n = 27; 50%); mean 2.1 ± 2.0 leads were removed per procedure/mean procedure-time was 100 ± 54 min. Local anesthetic (LA) was used for all (mean-dose: 33 ± 8 ml 1% lidocaine), IV drug-doses used (mean ± SD) were: midazolam: 3.95 ± 2.44 mg, diazepam: 4.69 ± 0.89 mg and fentanyl: 57 ± 40 µg. Complete lead-extraction was achieved in 110 (85%) leads, partial lead-extraction (<4 cm-fragment remaining) in 5 (4%) leads. Sedation-related hypotension requiring IV fluids occurred in 2 (managed without adverse-consequences) and hypoxia requiring additional airway-management in none. No procedural deaths occurred, one patient required emergency cardiac surgery for localized ventricular perforation, nine had minor complications (transient hypotension/bradycardia/pericardial effusion not requiring intervention). CONCLUSION: TLE undertaken using LA/conscious-sedation was safe/feasible in our series and associated with good clinical outcome/low procedural complications. Reduced risk of aerosolization of COVID-19 and quicker patient recovery/reduced anesthetic risk are potential benefits that warrant further study.

Impact of a high-density grid catheter on long-term outcomes for structural heart disease ventricular tachycardia ablation.

BACKGROUND: Substrate mapping has highlighted the importance of targeting diastolic conduction channels and late potentials during ventricular tachycardia (VT) ablation. State-of-the-art multipolar mapping catheters have enhanced mapping capabilities. The purpose of this study was to investigate whether long-term outcomes were improved with the use of a HD Grid mapping catheter combining complementary mapping strategies in patients with structural heart disease VT. METHODS: Consecutive patients underwent VT ablation assigned to either HD Grid, Pentaray, Duodeca, or point-by-point (PbyP) RF mapping catheters. Clinical endpoints included recurrent anti-tachycardia pacing (ATP), appropriate shock, asymptomatic non-sustained VT, or all-cause death. RESULTS: Seventy-three procedures were performed (33 HD Grid, 22 Pentaray, 12 Duodeca, and 6 PbyP) with no significant difference in baseline characteristics. Substrate mapping was performed in 97% of cases. Activation maps were generated in 82% of HD Grid cases (Pentaray 64%; Duodeca 92%; PbyP 33% (p = 0.025)) with similar trends in entrainment and pace mapping. Elimination of all VTs occurred in 79% of HD Grid cases (Pentaray 55%; Duodeca 83%; PbyP 33% (p = 0.04)). With a mean follow-up of 372 ± 234 days, freedom from recurrent ATP and shock was 97% and 100% respectively in the HD Grid group (Pentaray 64%, 82%; Duodeca 58%, 83%; PbyP 33%, 33% (log rank p = 0.0042, p = 0.0002)). CONCLUSIONS: This study highlights a step-wise improvement in survival free from ICD therapies as the density of mapping capability increases. By using a high-density mapping catheter and combining complementary mapping strategies in a strict procedural workflow, long-term clinical outcomes are improved.

Real-world evaluation of followup strategies after ICD therapies in patients with VT (REFINE-VT).

Implantable cardiac defibrillators (ICDs) can prevent sudden cardiac death, but the risk of recurrent ventricular arrhythmia (VA) and ICD shocks persist. Strategies to minimise such risks include medication optimisation, device programming and ventricular tachycardia (VT) ablation. Whether the choice of these interventions at follow-up are influenced by factors such as the type of arrhythmia or ICD therapy remains unclear. To investigate this, we evaluated ICD follow-up strategies in a real-world population with primary and secondary prevention ICDs. REFINE-VT (Real-world Evaluation of Follow-up strategies after Implantable cardiac-defibrillator therapies in patients with Ventricular Tachycardia) is an observational study of 514 ICD recipients recruited between 2018 and 2019. We found that 77 patients (15%) suffered significant VA and/or ICD therapies, of whom 26% experienced a second event; 31% received no intervention. We observed an inconsistent approach to the choice of strategies across different types of arrhythmias and ICD therapies. Odds of intervening were significantly higher if ICD shock was detected compared with anti-tachycardia pacing (odds ratio [OR] 8.4, 95% confidence interval [CI] 1.7 to 39.6, p=0.007). Even in patients with two events, the rate of escalation of antiarrhythmics or referral for VT ablation were as low as patients with single events. This is the first contemporary study evaluating how strategies that reduce the risk of recurrent ICD events are executed in a real-world population. Significant inconsistencies in the choice of interventions exist, supporting the need for a multi-disciplinary approach to provide evidence-based care to this population.

Outcome in patients undergoing upgrade to cardiac resynchronization therapy: predictors of outcome after upgrade to CRT.

The advantages of upgrade to cardiac resynchronisation therapy (CRT) have not been explored as carefully as the outcomes of de novo CRT implantations. Furthermore selection criteria for patients with the potential to benefit the most from this therapy are unknown. Therefore, we analyzed the long term outcome and its predictors in a real-world cohort receiving a CRT upgrade from previous pacemaker (PM) and defibrillator devices (ICD). We analyzed 86 patients (mean age 68 ± 9 years; 89% male) undergoing CRT upgrade procedures. Response to CRT as well as long term patient outcome was analyzed. NYHA class improved in majority of the patients during short term period (61%), and this trend remained constant during long term follow-up (54%). The observed all-cause mortality was 54% with mean survival of 49 ± 4 months. 11 patients underwent left ventricular assist device implantation or heart transplantation. In the multivariate analysis, only kidney function assessed by GFR (HR 0.97; 95% CI 0.95-0.99; p = 0.009) and LVEF (HR 0.92; 95% CI 0.87-0.97; p = 0.002) remain predictors for mortality. Patients who undergo an upgrade procedure to CRT demonstrate a significant response rate assessed by improvement in NYHA class, with initial baseline parameters such as LVEF and kidney function remaining significant predictors for mortality.

Pain During "Noncomplex" Electrophysiological Studies and Cardiac Rhythm Device Surgery.

BACKGROUND: There are only limited data about peri-interventional pain during cardiac electrophysiological procedures without analgosedation. In this study, peri-interventional pain and recollection of it after the intervention were evaluated. METHODS: A total of 101 patients (43 electrophysiological/ablation procedures and 58 device surgeries) reported pain on a numerical rating scale (NRS; 0-10) before (pre), during (peri), and after (post) the intervention. Maximum pain (maxNRS) and the average of pain (meanNRS) were used for statistical analysis. Peri-interventional pain was compared with postinterventional data of the recollection of peri-interventional pain (peri-post). Patients were allocated into 2 groups (with 51 and 50 patients, respectively) to evaluate the mode of patient-staff interaction on pain recollection. Depressive, anxiety, and somatic symptom scales (Patient Health Questionnaire-15, Generalized Anxiety Disorder-7, and Patient Health Questionnaire-15) were used to analyze their influence on pain recollection. RESULTS: In total, 49.6% of patients (n = 50) complained of moderate to severe pain (maxNRS) at least once during the procedure. The comparison between peri and peri-post data revealed the following (median (range)-maxNRS, peri: 3 (0-10) versus peri-post: 4 (0-9) (ns), and meanNRS, peri: 1.4 (0-7) versus peri-post: 2.0 (0-6) (ns). The mode of patient-staff interaction had no influence on pain. No effect was found for psychosocial factor concerning pain and the recollection of pain. The results of the linear regression showed no influence of low-dose midazolam on recollection of pain. CONCLUSION: Half of the patients reported moderate to severe pain at least once during cardiac electrophysiological procedures without analgosedation. However, on average, patients reported only low pain levels. Postinterventional derived data on discomfort reflect the peri-interventional situation.

Reversibility of severe mitral valve regurgitation after left ventricular assist device implantation: single-centre observations from a real-life population of patients.

OBJECTIVES: This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. METHODS: Of the 234 patients who received LVAD therapy in our centre during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7-28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283-848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. RESULTS: We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). CONCLUSIONS: Preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival.

Hypertrophic obstructive cardiomyopathy-the Leipzig experience.

BACKGROUND: Management of hypertrophic obstructive cardiomyopathy (HOCM) has evolved considerably over the last fifty years, and includes medical treatment as well as septal myectomy (SM) to relief symptoms caused by left ventricular outflow tract obstruction (LVOTO). We report the Leipzig Heart Center experience in the surgical management of patients with HOCM. METHODS: We collected data from all patient treated surgically with a myectomy for LVOTO in patients with HOCM between 1997 and 2016. Patients with absent data were excluded from our analysis. All data were obtained from our surgical database and analyzed retrospectively. RESULTS: We identified 115 patients who underwent surgical treatment for HOCM, where a male:female ratio of 1.1:1, a mean age of 60.8±14.6 years and a body mass index of 27.7±4.5 were observed. The most common symptom was dyspnea (n=102). Of all patients, 50% had New York Heart Association (NYHA) III class symptoms. Arterial hypertension was the most common comorbidity (n=80). Preoperative transthoracic echocardiography showed a mean ejection fraction (EF) of 65.9%±9.7%, median septal thickness of 21.1±5.3 mm, systolic anterior motion of the mitral valve (MV) in 61.7% of patients, and mean LVOT gradient of 70.1±45.2 mmHg. Surgery resulted in a mean decrease of the septal thickness by 15±3.7 mm and LVOT gradient by 9.7±8.5 mmHg. Isolated SM was carried out on 20 patients. Postoperatively, we were able to notice a significant improvement in NYHA classification, in which patients with NYHA III benefitted most from SM. Long-term follow-up data up to 11.3±0.7 years were available for 114 patients. During follow-up, 16 patients died, and one patient was lost to follow up. CONCLUSIONS: Surgical treatment of LVOT in patients with HOCM is an effective intervention that improves cardiac function and quality of life (QoL) and is associated with a low operative risk.