2024 Australia-New Zealand Expert Consensus Statement on Cardiac Amyloidosis.

Over the past 5 years, early diagnosis of and new treatments for cardiac amyloidosis (CA) have emerged that hold promise for early intervention. These include non-invasive diagnostic tests and disease modifying therapies. Recently, CA has been one of the first types of cardiomyopathy to be treated with gene editing techniques. Although these therapies are not yet widely available to patients in Australia and New Zealand, this may change in the near future. Given the rapid pace with which this field is evolving, it is important to view these advances within the Australian and New Zealand context. This Consensus Statement aims to update the Australian and New Zealand general physician and cardiologist with regards to the diagnosis, investigations, and management of CA.

Clinical Outcomes of Patients Treated With Pulmonary Vasodilators Early and in High Dose After Left Ventricular Assist Device Implantation.

Right ventricular failure (RVF) is common after left ventricular assist device (LVAD) implantation and a major determinant of adverse outcomes. Optimal perioperative right ventricular (RV) management is not well defined. We evaluated the use of pulmonary vasodilator therapy during LVAD implantation. We performed a retrospective analysis of continuous-flow LVAD implants and pulmonary vasodilator use at our institution between September 2004 and June 2013. Preoperative RVF risk was assessed using recognized variables. Sixty-five patients (80% men, 50 ± 14 years) were included: 52% HeartWare ventricular assist device (HVAD), 11% HeartMate II (HMII), 17% VentrAssist, 20% Jarvik. Predicted RVF risk was comparable with contemporary LVAD populations: 8% ventilated, 14% mechanical support, 86% inotropes, 25% BUN >39 mg/dL, 23% bilirubin ≥2 mg/dL, 31% RV : LV (left ventricular) diameter ≥0.75, 27% RA : PCWP (right atrium : pulmonary capillary wedge pressure) >0.63, 36% RV stroke work index <6 gm-m/m(2)/beat. The majority (91%) received pulmonary vasodilators early and in high dose: 72% nitric oxide, 77% sildenafil (max 200 ± 79 mg/day), 66% iloprost (max 126 ± 37 µg/day). Median hospital stay was 26 (21) days. No patient required RV mechanical support. Of six (9%) patients meeting RVF criteria based on prolonged need for inotropes, four were transplanted, one is alive with an LVAD at 3 years, and one died on day 35 of intracranial hemorrhage. Two-year survival was 77% (92% for HMII/HVAD): transplanted 54%, alive with LVAD 21%, recovery/explanted 2%. A low incidence of RVF and excellent outcomes were observed for patients treated early during LVAD implantation with combination, high-dose pulmonary vasodilators. The results warrant further investigation in a randomized controlled study.

Mycoplasma and Ureaplasma Donor-Derived Infection and Hyperammonemia Syndrome in 4 Solid Organ Transplant Recipients From a Single Donor.

Hyperammonemia syndrome (HS) is a life-threatening condition occurring in solid organ transplant patients, affecting primarily lung recipients, and is associated with Mycoplasma hominis and/or Ureaplasma spp infection. The organ donor was a young man who died of hypoxic brain injury and had urethral discharge antemortem. The donor and 4 solid organ transplant recipients had infection with M hominis and/or Ureaplasma spp. The lung and heart recipients both developed altered conscious state and HS associated with M hominis and Ureaplasma spp infections. Despite treatment with antibiotics and ammonia scavengers, both the lung and heart recipients died at day +102 and day +254, respectively. After diagnosis in the thoracic recipients, screening samples from the liver recipient and 1 kidney recipient were culture positive for M hominis with or without Ureaplasma spp. Neither the liver nor kidney recipients developed HS. Our case series demonstrates the unique finding of M hominis and Ureaplasma spp dissemination from an immunocompetent donor across 4 different organ recipients. Phylogenetic whole genome sequencing analysis demonstrated that M hominis samples from recipients and donor were closely related, suggesting donor-derived infection. Screening of lung donors and/or recipients for Mycoplasma and Ureaplasma spp is recommended, as well as prompt treatment with antimicrobials to prevent morbidity.

Post-Myocardial Infarction Ventricular Septal Defect Successfully Treated with Impella as Bridge to Cardiac Transplantation.

A 63-year-old female presented late with anterior ST-elevation myocardial infarction and cardiogenic shock. This was complicated by acute ventricular septal defect with large left-to-right shunt. An Impella CP was inserted on day seven with rapid haemodynamic improvement. This facilitated bridge to cardiac transplant on day twelve post-MI.

Left Atrial Intramural Hematoma Post-Ablation of Supraventricular Tachycardia: A Rare Complication Treated Successfully.

We report successful management of left atrial hematoma after ablation of supraventricular tachycardia. A 43-year-old female patient experienced chest pain immediately after radiofrequency ablation of a symptomatic left posterolateral accessory pathway. Transthoracic echocardiography demonstrated a large mass occupying the left atrium. Computed tomography and transesophageal echocardiography results were consistent with posterolateral intramural hematoma. She became hemodynamically unstable, requiring emergent surgery. The mass resolved completely by 6 weeks. (Level of Difficulty: Beginner.).

Cardiovascular Testing Detects Underlying Dysfunction in Childhood Leukemia Survivors.

PURPOSE: Childhood leukemia survivors commonly develop late-onset cardiovascular disease after treatment with anthracyclines. Resting echocardiogram is the standard procedure for monitoring cardiac health but this method may not be sensitive enough to detect subclinical injury. Exercise echocardiography may provide a viable alternative. METHODS: Nineteen (9 males; age, 19 ± 3 yr) anthracycline-treated survivors of childhood leukemia and 17 (8 males) healthy individuals of similar age (22 ± 2 yr) were recruited. All survivors had normal resting echocardiography upon recruitment. Exercise echocardiography was performed using contemporary imaging techniques. Flow-mediated dilation (FMD), body composition, and cardiorespiratory fitness (V˙O2peak) were assessed to determine predisposition to additional disease. RESULTS: Mitral valve peak flow velocity in late diastole (interaction, P = 0.007) increased from rest in survivors (P = 0.023) and controls (P = 0.020) immediately postexercise but did not recover again in the survivors (exercise-recovery, P = 0.784) after recuperation. Consequently, E/A ratio (interaction, P < 0.001) was lower in the survivors at recovery (P < 0.001). Survivors had reduced FMD (7.88 ± 1.70 vs 9.65 ± 2.83; P = 0.030), maximal and recovery HR (P = 0.001; P < 0.001), minute ventilation (P < 0.001), and V˙O2peak (absolute, 2.64 ± 0.62 vs 3.14 ± 0.74 L·min, P = 0.034; relative, 36.78 ± 11.49 vs 45.14 ± 6.80 mL·kg·min; P = 0.013) compared with controls. They also had higher total body fat (percentage, P = 0.034; mass, P = 0.024) and fat mass in the central (P = 0.050), peripheral (P = 0.039) and visceral (P < 0.001) regions. Survivors matched controls with regard to height (173.0 ± 7.8 cm vs 173.8 ± 9.1 cm; P = 0.796), body mass (76.16 ± 19.05 kg vs 70.07 ± 13.96 kg; P = 0.287) and body mass index (25.2 ± 5.1 vs 22.9 ± 2.7; P = 0.109). CONCLUSIONS: Exercise echocardiography unmasked subclinical diastolic dysfunction that may indicate late anthracycline toxicity in apparently healthy survivors of childhood leukemia. Presence of secondary risk factors indicates increased predisposition to comorbidities and highlights the importance of assessing cardiovascular health during follow-up.

The Impact of Distinct Exercise Training Modalities on Echocardiographic Measurements in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Exercise training is an important component of multidisciplinary heart failure management. However, the effects of aerobic training (AT) versus resistance training (RT) on cardiac function in patients with heart failure with reduced ejection fraction are not well defined. The aim of this study was to evaluate the impact of these exercise modalities on echocardiographic parameters. METHODS: Participants with stable heart failure with reduced ejection fraction (ejection fraction < 50%) were randomized to 12 weeks of AT, RT, or untrained control. Exercise was performed at matched relative intensities of each training modality (50%-70% of maximum). Echocardiography and cardiopulmonary exercise testing were performed at baseline and after 12 weeks of training. RESULTS: Thirty-eight participants were randomized, and 12 in each group completed the intervention (mean age, 61.5 ± 1.7 years; 89% men). Peak oxygen consumption increased from 14.5 ± 1.3 to 17.2 ± 1.6 ml · min-1 · kg-1 after AT and from 13.7 ± 1.2 to 16.4 ± 1.1 ml · min-1 · kg-1 after RT (P < .001 for both). In the AT group, there was a decrease in septal e' (from 0.052 ± 0.004 to 0.041 ± 0.004 m/sec) and increases in E/e' ratio (from 18.2 ± 3.1 to 23.8 ± 3.5), left atrial volume (from 86 ± 9 to 99 ± 10 mL), and right ventricular end-diastolic area (from 18 ± 1 to 20 ± 1 cm2; P < .05 for all), but these were unchanged in the control and RT groups. There were no significant changes in left ventricular diameters or volumes or right ventricular fractional area change after exercise. CONCLUSIONS: There is a differential effect of AT versus RT on some echocardiographic parameters in patients with heart failure with reduced ejection fraction. AT was associated with evidence of worsening myocardial diastolic function, whereas this was not apparent after RT. Further studies are indicated to investigate the long-term clinical significance of these adaptations.

High-intensity interval training in patients with left ventricular assist devices: A pilot randomized controlled trial.

BACKGROUND: Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure. To date, studies evaluating the impact of aerobic training in patients with LVADs have focused on moderate-intensity exercise. METHODS: This pilot randomized controlled trial compared the effects of high-intensity interval training (HIIT) with those of moderate-intensity continuous training (MICT) on peak oxygen consumption (V̇O2 peak) in patients with LVADs. Secondary outcomes included 6-minute walk test distance, flow-mediated dilation, and anthropometry. Assessments were conducted at baseline and after 12 weeks of supervised training performed 3 times weekly. Participants were randomized to HIIT (4 sets of 4 minutes at 80%-90% V̇O2 reserve, alternating with 3 minutes at 50%-60% V̇O2 reserve) or MICT groups (28 minutes continuously at 50%-60% V̇O2 reserve). Within and between-group differences were analyzed using linear mixed models. Data are expressed as marginal means with 95% confidence intervals or as mean ± SD. RESULTS: A total of 21 participants were randomized (HIIT: age 57.7 ± 13.1 years; n = 11 and MICT: age 55.6 ± 14.2 years; n = 10) (mean ± SD). No major adverse events occurred in response to training in either group. HIIT significantly improved V̇O2 peak (15.6 [13.2-17.8] to 18.4 [16.0-20.8] ml/kg/min) (marginal mean [95% CI]) compared with MICT (16.2 [13.8-18.7] to 17.2 [14.6-19.7] ml/kg/min; p < 0.05 between groups). No significant group differences were detected in secondary outcomes. CONCLUSION: In patients with LVADs, HIIT was well tolerated and increased aerobic capacity more than MICT. These preliminary findings support the prescription of high-intensity exercise in clinically stable patients with LVADs but warrant validation in a larger sample and across a broader range of physiologic and clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au, unique identifier: ACTRN12616001596493.

The impact of exercise training on conduit artery wall thickness and remodeling in chronic heart failure patients.

Exercise training is an important adjunct to medical therapy in chronic heart failure, but the extent to which exercise impacts on conduit artery remodeling is unknown. The aim of this study was to evaluate the impact of aerobic and resistance exercise training modalities on arterial remodeling in patients with chronic heart failure. We randomized 36 untrained subjects with chronic heart failure to resistance training (58.8 ± 3.5 years), aerobic training (61.3 ± 2.8 years), or an untrained control group (64.4 ± 2.4 years). Peak oxygen consumption during cycle ergometry increased after 12 weeks in both the resistance and aerobic training (P < 0.001) groups, but not in controls, whereas leg strength only increased after resistance training (P < 0.05). Brachial artery wall thickness decreased in the resistance training group (475 ± 10 versus 443 ± 13 µm; P < 0.01), whereas no changes were apparent in the aerobic or control groups. Brachial diameter increased by ≈6% and ≈5% in the aerobic training and resistance training groups (P < 0.01), with no change evident in the control group. The wall:lumen ratio consequently declined in the resistance training group at 12 weeks (0.121 ± 0.004 versus 0.107 ± 0.004; P < 0.01) and increased in the control group (0.111 ± 0.006 versus 0.121 ± 0.009; P < 0.05). No wall:lumen change was evident in the aerobic training group. Our findings suggest that exercise has a systemic impact on remodeling of conduit arteries in humans and that resistance exercise training may be advantageous in subjects with chronic heart failure in this regard.

Polymer injection therapy to reverse remodel the papillary muscles: efficacy in reducing mitral regurgitation in a chronic ischemic model.

BACKGROUND: Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. METHODS AND RESULTS: Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm(2)to 7.6±1.3 cm(2), P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, τ (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). CONCLUSIONS: PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.

The use of exercise echocardiography in the evaluation of mitral regurgitation.

Mitral regurgitation (MR) is the second most common valvular disease in western countries after aortic stenosis. Optimal management of patients with MR depends on the etiology of the regurgitation and is based predominantly on left ventricular function and functional status. Recent outcome studies report high risk subsets of asymptomatic patients with MR, and practice guidelines underscore the importance of a well-established estimation of exercise tolerance and recommend exercise testing to objectively assess functional status and hemodynamic factors.

Observations from non-invasive measures of right heart hemodynamics in left ventricular assist device patients.

BACKGROUND: Left ventricular assist devices (LVADs) reduce pulmonary vascular resistance (PVR) in patients with severe heart failure. The aim of this study was to noninvasively assess the effect of LVAD implantation on PVR and right-heart function. METHODS: In 21 patients with HeartMate II LVADs, serial echocardiograms were reviewed prior to implantation and 1 and 6 months after implantation. Echocardiographic and Doppler indices of right-heart structure and function were measured along with LVAD settings, hemodynamics, and biochemistry, and the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and 6-minute walk test were administered. RESULTS: Comparing values before and 1 month after implantation, there were reductions in PVR (3.51 +/- 0.9 vs 2.0 +/- 0.5 Wood units, P < .0001), right ventricular (RV) systolic pressure (49 +/- 11 vs 34 +/- 7 mm Hg, P < .0001), and tricuspid regurgitation severity, with no change in RV size, RV fractional area change, or tricuspid annular plane systolic excursion. Patients with larger PVR reductions had better clinical status (MLHFQ score, 28 +/- 12 vs 60 +/- 29, P = .04; 6-minute walking distance, 1706 +/- 71 vs 1141 +/- 387 ft, P = .04). Patients with significant deteriorations in RV function had poorer clinical status (MLHFQ score, 79 +/- 13 vs 51 +/- 27, P = .04; 6-minute walking distance, 480 +/- 275 vs 1030 +/- 437 ft, P = .04). CONCLUSIONS: Echocardiographically detected changes in right-heart hemodynamics were associated with symptomatic status after LVAD implantation.