HeartMate 3 biventricular support exceeding 4.5 years.

A 47-year old male with ischaemic cardiomyopathy was referred to us for durable left ventricular assist device placement. He was found to have prohibitively elevated pulmonary vascular resistance for heart transplantation. He underwent HeartMate 3 left ventricular assist device implantation, with additional temporary right ventricular assist device (RVAD) placement. Following a 2-week period of unweanable temporary right ventricular support, the patient was switched to durable biventricular support with two Heartmate 3 pumps. The patient was placed on a transplant waiting list but was not offered a heart for over 4 years. While on Heartmate 3 biventricular support (BiVAD), he returned to full activity and enjoyed an excellent quality of life. He underwent laparoscopic cholecystectomy 7 months after the BIVAD implant. After 52 months of uneventful BiVAD support, he presented with a combination of adverse events that occurred over a short period. These included subarachnoidal haemorrhage and a new motor deficit, followed by RVAD infection and RVAD low-flow alarms. After over 4 years of unimpeded RVAD flows, new imaging revealed an outflow graft twist with subsequent flow reduction. The patient underwent heart transplantation after a total of 1655 days of Heartmate 3 BiVAD support and continues to do well on latest follow-up.

Sequencing and titrating approach of therapy in heart failure with reduced ejection fraction following the 2021 European Society of Cardiology guidelines: an international cardiology survey.

AIMS: In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists. METHODS AND RESULTS: An independent academic web-based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide 1 year after the publication of the latest European HF guidelines. Overall, 615 cardiologists (38 [32-47] years old, 63% male) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was ≤40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors first (74%), beta-blockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium-glucose cotransporter 2 inhibitors (53%) fourth. Eighty-four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers. CONCLUSION: In a broad international cardiology community, the 'historical approach' to HFrEF therapies remains the preferred sequencing approach. However, accelerated introduction and uptitration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices.

How does age affect outcomes after left ventricular assist device implantation: results from the PCHF-VAD registry.

AIMS: Use of left ventricular assist devices (LVADs) in older patients has increased, and assessing outcomes in older LVAD recipients is important. Therefore, this study aimed to investigate associations between age and outcomes after continuous-flow LVAD (cf-LVAD) implantation. METHODS AND RESULTS: Cf-LVAD patients from the multicentre European PCHF-VAD registry were included and categorized into those <50, 50-64, and ≥65 years old. The primary endpoint was all-cause mortality. Among secondary outcomes were heart failure (HF) hospitalizations, right ventricular (RV) failure, haemocompatibility score, bleeding events, non-fatal thromboembolic events, and device-related infections. Of 562 patients, 184 (32.7%) were <50, 305 (54.3%) were aged 50-64, whereas 73 (13.0%) were ≥65 years old. Median follow-up was 1.1 years. Patients in the oldest age group were significantly more often designated as destination therapy (DT) candidates (61%). A 10 year increase in age was associated with a significantly higher risk of mortality (hazard ratio [HR] 1.34, 95% confidence interval [CI] [1.15-1.57]), intracranial bleeding (HR 1.49, 95% CI [1.10-2.02]), and non-intracranial bleeding (HR 1.30, 95% CI [1.09-1.56]), which was confirmed by a higher mean haemocompatibility score (1.37 vs. 0.77, oldest vs. youngest groups, respectively, P = 0.033). Older patients suffered from less device-related infections requiring systemic antibiotics. No age-related differences were observed in HF-related hospitalizations, ventricular arrhythmias, pump thrombosis, non-fatal thromboembolic events, or RV failure. CONCLUSIONS: In the PCHF-VAD registry, higher age was associated with increased risk of mortality, and especially with increased risk of major bleeding, which is particularly relevant for the DT population. The risks of HF hospitalizations, pump thrombosis, ventricular arrhythmia, or RV failure were comparable. Strikingly, older patients had less device-related infections.

Sex-related differences in left ventricular assist device utilization and outcomes: results from the PCHF-VAD registry.

AIMS: Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort. METHODS AND RESULTS: This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure, bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess associations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant, women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2 (55% vs. 41%, P = 0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P = 0.001). Mean age was comparable (52.1 vs. 53.4 years, P = 0.33), and median follow-up duration was 344 [range 147-823] days for women and 435 [range 190-816] days for men (P = 0.40). No significant sex-related differences were found in all-cause mortality (hazard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50-1.27]). Female LVAD patients had a lower risk of ventricular arrhythmias (HR 0.56, 95% CI [0.33-0.95]) but more often experienced right ventricular failure. No significant sex-related differences were found in other outcomes. CONCLUSIONS: In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implantation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in female patients is warranted.

Impact of progressive aortic regurgitation on outcomes after left ventricular assist device implantation.

Aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) may adversely impact outcomes. We aimed to assess the incidence and impact of progressive AR after cf-LVAD on prognosis, biomarkers, functional capacity and echocardiographic findings. In an analysis of the PCHF-VAD database encompassing 12 European heart failure centers, patients were dichotomized according to the progression of AR following LVAD implantation. Patients with de-novo AR or AR progression (AR_1) were compared to patients without worsening AR (AR_0). Among 396 patients (mean age 53 ± 12 years, 82% male), 153 (39%) experienced progression of AR over a median of 1.4 years on LVAD support. Before LVAD implantation, AR_1 patients were less frequently diabetic, had lower body mass indices and higher baseline NT-proBNP values. Progressive AR did not adversely impact mortality (26% in both groups, HR 0.91 [95% CI 0.61-1.36]; P = 0.65). No intergroup variability was observed in NT-proBNP values and 6-minute walk test results at index hospitalization discharge and at 6-month follow-up. However, AR_1 patients were more likely to remain in NYHA class III and had worse right ventricular function at 6-month follow-up. Lack of aortic valve opening was related to de-novo or worsening AR (P < 0.001), irrespective of systolic blood pressure (P = 0.67). Patients commonly experience de-novo or worsening AR when exposed to continuous flow of contemporary LVADs. While reducing effective forward flow, worsening AR did not influence survival. However, less complete functional recovery and worse RV performance among AR_1 patients were observed. Lack of aortic valve opening was associated with progressive AR.

Improved survival of left ventricular assist device carriers in Europe according to implantation eras: results from the PCHF-VAD registry.

AIMS: Temporal changes in patient selection and major technological developments have occurred in the field of left ventricular assist devices (LVADs), yet analyses depicting this trend are lacking for Europe. We describe the advances of European LVAD programmes from the PCHF-VAD registry across device implantation eras. METHODS AND RESULTS: Of 583 patients from 13 European centres in the registry, 556 patients (mean age 53 ± 12 years, 82% male) were eligible for this analysis. Patients were divided into eras (E) by date of LVAD implantation: E1 from December 2006 to December 2012 (6 years), E2 from January 2013 to January 2020 (7 years). Patients implanted more recently were older with more comorbidities, but less acutely ill. Receiving an LVAD in E2 was associated with improved 1-year survival in adjusted analysis (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.98; p = 0.043). LVAD implantation in E2 was associated with a significantly lower chance of heart transplantation (adjusted HR 0.40, 95% CI 0.23-0.67; p = 0.001), and lower risk of LVAD-related infections (adjusted HR 0.64, 95% CI 0.43-0.95; p = 0.027), both in unadjusted and adjusted analyses. The adjusted risk of haemocompatibility-related events decreased (HR 0.60, 95% CI 0.39-0.91; p = 0.016), while heart failure-related events increased in E2 (HR 1.67, 95% CI 1.02-2.75; p = 0.043). CONCLUSION: In an analysis depicting the evolving landscape of continuous-flow LVAD carriers in Europe over 13 years, a trend towards better survival was seen in recent years, despite older recipients with more comorbidities, potentially attributable to increasing expertise of LVAD centres, improved patient selection and pump technology. However, a smaller chance of undergoing heart transplantation was noted in the second era, underscoring the relevance of improved outcomes on LVAD support.

Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices: insights from TRAViATA.

BACKGROUND: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs. METHODS: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111). RESULTS: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D. CONCLUSION: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV­lead pacing post LVAD implantation.

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

BACKGROUND: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. METHODS: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. RESULTS: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. CONCLUSIONS: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.

Cardiac implantable electronic devices with a defibrillator component and all-cause mortality in left ventricular assist device carriers: results from the PCHF-VAD registry.

AIMS: To compare characteristics of left ventricular assist device (LVAD) recipients receiving a cardiac implantable electronic device (CIED) with a defibrillator component (implantable cardioverter-defibrillator and cardiac resynchronization therapy with defibrillation, CIED-D) vs. those without one, and to assess whether carrying such a device contiguously with an LVAD is associated with outcomes. METHODS AND RESULTS: Overall, 448 patients were analysed (mean age 52 ± 13 years, 82% male) in the multicentre European PCHF-VAD registry. To account for all active CIED-Ds during ongoing LVAD treatment, outcome analyses were performed by a time-varying analysis with active CIED-D status post-LVAD as the time-varying covariate. At the time of LVAD implantation, 235 patients (52%) had an active CIED-D. Median time on LVAD support was 1.1 years (interquartile range 0.5-2.0 years). A reduction of 36% in the risk of all-cause mortality was observed in patients with an active CIED-D [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.46-0.91; P = 0.012), increasing to 41% after adjustment for baseline covariates (HR 0.59, 95% CI 0.40-0.87; P = 0.008) and 39% after propensity score adjustment (HR 0.61, 95% CI 0.39-0.94; P = 0.027). Other than CIED-D, age, LVAD implant as redo surgery, number of ventricular arrhythmia episodes and use of vasopressors pre-LVAD were remaining significant risk factors of all-cause mortality. Incident ventricular arrhythmias post-LVAD portended a 2.4-fold and 2.6-fold increased risk of all-cause and cardiovascular death, respectively; carrying an active CIED-D remained associated with a 47% and 43% reduction in these events, respectively. CONCLUSIONS: In an analysis accounting for all active CIED-Ds, including those implanted during LVAD support, carrying such a device was associated with significantly better survival during LVAD support.

Microcirculation and Heart Failure.

The idea of coronary microcirculation playing a role in the pathophysiology of heart failure dates from decades ago, with authors hypothesizing that structural and functional alterations in the coronary microcirculation could potentially contribute to heart failure. It is known that in a wide range of primary cardiomyopathies, from dilated to hypertrophic, there are pathological alterations in myocardial vasculature structure and function, playing a role in the clinical course of the disease. Needless to say, many patients with normal epicardial coronary arteries can suffer from coronary microvascular dysfunction, that could lead to a wide variety of clinical problems - from impaired functional capacity to stable and unstable angina, Takotsubo syndrome, myocardial infarction with normal coronary arteries and can also end up with either acute or chronic heart failure. Furthermore, nowadays, it has been recognized that pathophysiology of the heart failure with preserved ejection fraction (HFpEF) is mainly due to the myocardial microcirculatory impairment. In heart failure with reduced ejection fraction (HFrEF) neurohumoral mechanisms affecting the peripheral vasculature have been identified as important factors in the development and progression of heart failure, leading to unfavourable remodelling, and thus some of them being important treatment targets. Among many new clinical scenarios where both myocardial and peripheral microcirculation play an important role, raising field of implantable continuous flow assist devices opens many questions and implies better understanding of their effects of microcirculation, as they usually lead to the improvement of end organ dysfunction caused by previous heart failure, which is probably through the positive effects of peripheral microcirculation.

Further insights into blood pressure induced premature beats: Transient depolarizations are associated with fast myocardial deformation upon pressure decline.

BACKGROUND: An acute increase in blood pressure is associated with the occurrence of premature ventricular complexes (PVCs). OBJECTIVE: We aimed to study the timing of these PVCs with respect to afterload-induced changes in myocardial deformation in a controlled, preclinically relevant, novel closed-chest pig model. METHODS: An acute left ventricular (LV) afterload challenge was induced by partial balloon inflation in the descending aorta, lasting 5-10 heartbeats (8 pigs; 396 inflations). RESULTS: Balloon inflation enhanced the reflected wave (augmentation index 30% ± 8% vs 59% ± 6%; P < .001), increasing systolic central blood pressure by 35% ± 4%. This challenge resulted in a more abrupt LV pressure decline, which was delayed beyond ventricular repolarization (rate of pressure decline 0.16 ± 0.01 mm Hg/s vs 0.27 ± 0.04 mm Hg/ms; P < .001 and interval T-wave to peak pressure 1 ± 12 ms vs 36 ± 9 ms; P = .008), during which the velocity of myocardial shortening at the basal septum increased abruptly (ie, postsystolic shortening) (peak strain rate -0.6 ± 0.5 s(-1) vs -2.5 ± 0.8 s(-1); P < .001). It is exactly at this time of LV pressure decline, with increased postsystolic shortening, and not at peak pressure, that PVCs occur (22% of inflations). These PVCs preferentially occurred at the basal and apical segments. In the same regions, monophasic action potentials demonstrated the appearance of delayed afterdepolarization-like transient depolarizations as origin of PVCs. CONCLUSION: An acute blood pressure increase results in a more abrupt LV pressure decline, which is delayed after ventricular repolarization. This has a profound effect on myocardial mechanics with enhanced postsystolic shortening. Coincidence with induced transient depolarizations and PVCs provides support for the mechanoelectrical origin of pressure-induced premature beats.