Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial.

BACKGROUND: Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction. METHODS: In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right-sided heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents. RESULTS: We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1-0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, -2 mm Hg [95% CI, -4 to -1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (-3 mm Hg [95% CI, -5 to -1] ) and higher mean CO (0.5 L/min [95% CI, 0.1-0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, -98 ng/L [95% CI, -185 to -23]), higher left ventricular ejection fraction (37±5 versus 34±5%; P=0.01), and lower left atrial and ventricular volumes. CONCLUSIONS: KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05161650.

Myocardial work across different etiologies of right ventricular dysfunction and healthy controls.

Evaluating right ventricular (RV) function remains a challenge. Recently, novel echocardiographic assessment of RV myocardial work (RVMW) by non-invasive pressure-strain loops was proposed. This enables evaluation of right ventriculoarterial coupling and quantifies RV dyssynchrony and post-systolic shortening. We aimed to assess RVMW in patients with different etiologies of RV dysfunction and healthy controls. We investigated healthy controls (n=17), patients with severe functional tricuspid regurgitation (FTR; n=22), and patients with precapillary pulmonary hypertension (PCPH; n=20). Echocardiography and right heart catheterization were performed to assess 1) RV global constructive work (RVGCW; work needed for systolic myocardial shortening and isovolumic relaxation), 2) RV global wasted work (RVGWW; myocardial shortening following pulmonic valve closure), and 3) RV global work efficiency (RVGWE; describes the relation between RV constructive and wasted work). RVGCW correlated with invasive RV stroke work index (r=0.66, P<0.001) and increased in tandem with higher afterload, i.e., was low in healthy controls (454±73 mmHg%), moderate in patients with FTR (687±203 mmHg%), and highest among patients with PCPH (881±255 mmHg%). RVGWE was lower and RVGWW was higher in patients with FTR (86±8% and 91 mmHg% [53-140]) or PCPH (86±10% and 110 mmHg% [66-159]) as compared with healthy controls (96±3% and 10 mmHg%). RVMW by echocardiography provides a promising index of RV function to discriminate between patients with RV volume or pressure overload. The prognostic value of this measure needs to be settled in future studies.

Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo. METHODS: In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level. RESULTS: A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients. CONCLUSIONS: In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.).

Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis.

BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. METHODS: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months. RESULTS: A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group. CONCLUSIONS: In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).

Wild-type transthyretin amyloid cardiomyopathy: expect the unexpected-a case report.

Background: General interest and incidence are increasing in wild-type transthyretin amyloidosis (ATTRwt) in recent time. As patient population increases, further knowledge of the management of the frequently encountered interacting cardiac comorbidities is requested to improve treatment of ATTRwt patients. Case summary: A 73-year-old male ATTRwt patient presented to the outpatient clinic (Day 0) with dyspnoea, leg swelling, and palpitations. At diagnosis, 3 years prior to presentation, he exhibited only minor signs of ATTRwt. At Day 0, clinical examination revealed atrial fibrillation and mild peripheral oedema. Anticoagulant and symptomatic treatment with beta-blocker and diuretics was initiated, and the patient was planned for sub-acute direct cardioversion, and the patient was discharged with a Holter monitor to outpatient care. At Day 7, analysis of the monitoring demonstrated spontaneous conversion to sinus rhythm and, unexpectedly, episodes of high-rate self-remittent sustained monomorphic ventricular tachycardia (VT) and frequent ventricular ectopic beats. At Day 8, a sub-acute coronary angiography was performed which revealed a significant proximal left anterior descending artery stenosis which was treated with percutaneous coronary intervention (PCI) and subsequently an internal defibrillator was implanted. Following visits at 1- and 3-month post-PCI at the outpatient clinic revealed no VT and suppression of ventricular ectopic beats. Discussion: The case illustrates some of the frequently encountered cardiac comorbidities (e.g. atrial fibrillation, ventricular arrhythmia, and ischaemic heart disease) associated with ATTRwt. A high level of suspicion is warranted to identify treatable cardiac conditions [atrial fibrillation, atrioventricular (AV) block, and ischaemic heart disease] and to uncover potentially fatal cardiac conditions in patients with ATTRwt.

Strain-derived myocardial work in wild-type transthyretin cardiac amyloidosis with aortic stenosis-diagnosis and prognosis.

BACKGROUND: Several echocardiographic parameters have been suggested to differentiate wild-type transthyretin cardiac amyloidosis (ATTRwt) from other causes of hypertrophy. These studies have all been performed in small samples of mixed cardiac amyloidosis. The purpose of this study was to investigate the role of echocardiographic parameters in patients with ATTRwt and aortic stenosis (AS) versus patients with AS. The secondary aim was to investigate the role of myocardial work in the prognosis of patients with ATTRwt. METHODS: The sensitivity and specificity of the relative apical sparing ratio (RAS), the apical-to-basal ratio (AB), the ejection-fraction-to-global-longitudinal-strain ratio (EF/GLS), and the global myocardial work index (GWI) were calculated using receiver-operated characteristics curves and area under the curve (AUC) in patients with ATTRwt and AS (n = 50) versus patients with AS (n = 354). Multivariable regression was used to assess the prognostic value of GWI in patients with ATTRwt (n = 212). RESULTS: When used to identify AS from ATTRwt + AS, GWI had a sensitivity of 80% and specificity of 70%. The AUC of GWI was larger than that of AB (p = .01) and EF/GLS (p > .01) but not RAS (p = .15). In patients with ATTRwt multivariable regression found age predicted mortality with an estimate of HR = 1.086 (CI: 1.034-1.141) while GWI predicted survival with an estimate of HR = .837 (CI: .733-.956) per 100 mmHg*% increase. CONCLUSION: GWI was demonstrated to be a viable classifier in ATTRwt and AS versus AS. GWI was demonstrated to independently predict survival in patients with ATTRwt. Further studies examining the role of myocardial work in ATTRwt are warranted.

Clinical characteristics and prognostic implications of orthopedic ligament disorders in patients with wild-type transthyretin amyloidosis cardiomyopathy.

BACKGROUND: Wild-type transthyretin amyloidosis (ATTRwt) is associated with multiple ligament disorders (LD) such as carpal tunnel syndrome (CTS), lumbar spinal stenosis (LSS), and spontaneous tendon rupture (STR). No studies have investigated the prevalence of these LD in the same cohort of ATTRwt patients. Furthermore, the clinical characteristics and prognostic implications of such disorders have not been studied. METHODS: From 2017 to 2022, 206 consecutive patients with ATTRwt were diagnosed and followed prospectively to the time of death or the censoring date of September 1st, 2022. Patients with and without LD were compared, and the presence of LD was used along with the baseline clinical, biochemical, and echocardiographic characteristics to predict hospitalization with worsening heart failure and death. RESULTS: CTS surgery was performed in 34 % of the patients, 8 % were treated for LSS, and 10 % had experienced an STR. The median follow-up time was 706 days (312-1067). Hospitalization with worsening heart failure occurred more frequently in patients with LD compared to patients without LD (p = 0.035). Presence of LD or surgery for CTS were found to be independent predictors of worsening heart failure with a hazard ratio of 2.0 (p = 0.01). The mortality was comparable between patients with and without LD (p = 0.10). CONCLUSION: Orthopedic disorders are prevalent in ATTRwt cardiomyopathy, and presence of LD was an independent predictor of hospitalization with worsening heart failure.

Does targeted positioning of the left ventricular pacing lead towards the latest local electrical activation in cardiac resynchronization therapy reduce the incidence of death or hospitalization for heart failure?

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. METHODS: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. CONCLUSIONS: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. GOV IDENTIFIER: NCT03280862.

Association of Right Ventricular Myocardial Blood Flow With Pulmonary Pressures and Outcome in Cardiac Amyloidosis.

BACKGROUND: Cardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied. OBJECTIVES: This study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA. METHODS: Cardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11C-acetate, 15O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA. RESULTS: MBF of the right ventricle (MBFRV) and the ratio of MBFRV and MBF of the left ventricle (MBFRV/LV) for the 2 tracers were significantly correlated (r > 0.92). MBFRV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBFLV was inversely correlated with wall thickness (P < 0.0001). MBFRV/LV was significantly associated with N-terminal pro-B-type natriuretic peptide levels, NYHA functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBFRV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with HR: 9.0 (95% CI: 4.2-14.5), P < 0.0001). CONCLUSIONS: Measurements of MBFRV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis.

Health-related quality of life among transthyretin amyloid cardiomyopathy patients.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR CM) is a progressive and severe heart disease with physical and psychological implications. The Nordic PROACT study was conducted to investigate the health-related quality of life (HRQoL) in ATTR CM patients. METHODS AND RESULTS: The Nordic PROACT study was a cross-sectional non-interventional study conducted in 12 cardiology hospital clinics across Norway, Sweden, Finland and Denmark. Men and women aged ≥18 years diagnosed with symptomatic ATTR CM were included. The investigator provided information on medical history, biomarkers, current treatment, co-morbidities and disease severity according to the New York Heart Association (NYHA) class and the National Amyloidosis Centre (NAC) staging. Patients completed the HRQoL questionnaires in the form of the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D-5L index with Visual Analog Scale (VAS), and the Major Depression Inventory (MDI). A total of 169 patients (mean ± SD age 77.7 ± 6.2 years) were included. Ninety-two per cent were men. Seventy-six per cent had wildtype ATTR CM (ATTRwt CM) and 15% had a hereditary form of ATTR CM (ATTRv CM) while 9% were genetically unclassified. Most patients were in NYHA class II (54%) and NAC stage 1 (53%). Participation in randomized clinical trials (RCT) was noted in 58% of the patients. The 169 ATTR CM patients had a mean ± SD KCCQ score of 64.3 ± 23.1 for total symptom score, 64.8 ± 20.9 for overall summary score (OSS) and 65.1 ± 21.5 for clinical summary score. The EQ-5D-5L total utility score was 0.8 ± 0.2 and the EQ-5D-5L VAS score was 62.9 ± 20.6. The vast majority (89%) did not report any signs of depression. Patients with ATTRv CM had a higher KCCQ OSS as compared with ATTRwt CM, while EQ-5D-5L utility score, EQ-5D-5L VAS and MDI were similar. Non-RCT participants had a poorer HRQoL as compared with RCT participants as reflected in lower KCCQ OSS and EQ-5D-5L VAS scores and a higher MDI score. Patients with higher NYHA classes and NAC disease stages had a poorer HRQoL as demonstrated by lower KCCQ and EQ-5D-5L scores and higher MDI scores. Correlation between KCCQ, EQ-5D-5L and MDI and the covariate NYHA class remained significant (P < 0.05) after adjusting for multiple testing. CONCLUSIONS: KCCQ scores were lower than previously reported for patients with other heart diseases of non-ATTR CM origin. The HRQoL measures correlated well to NYHA class and NAC disease stage. The prevalence of depression appeared to be low.

Prognostic implications of residual left ventricular hypertrophy and systolic dysfunction in aortic stenosis following transcatheter aortic valve replacement.

The impact of left ventricle (LV) hypertrophy (LVH) regression on contractility-associated measures, the extent of residual cardiac dysfunction and prognostic implications after the initial remodeling process after transcatheter aortic valve replacement (TAVR) has not been investigated. We aimed to assess whether greater LV mass regression from pre-TAVR to 12-months after TAVR was associated with increased systolic function; and assess the prognostic value of residual LVH, systolic function and contractility-associated measures 12-months after TAVR. A total of 439 symptomatic patients were included and examined by echocardiography. LVH regression was assessed as percentage change in LV mass index (LVMi) from baseline to 12-months after TAVR. Midwall fractional shortening (mFS) and stress-corrected (SC-mFS) were used as contractility-associated measures. Primary outcome was all-cause mortality. SC-mFS increased from 0.94 (0.7) at baseline (BS) to 1.22 (0.7) (p < 0.05) 12-months after TAVR for patients with the most LVH regression, compared to patients with no LV regression (BS 1.06 (0.7) to 1.04 (0.5), NS). At 12-months after TAVR, multivariate analysis showed independent prognostic value of LVEF < 50% or GLS < 15% (HR 1.59, p = 0.049) and mFS < 14% (HR 1.99, p = 0.002) for future all cause death. LVH regression in AS after TAVR is associated with significant improvements of LV systolic function in contrast to patients without LV regression. Residual LVH and subsequent LV systolic dysfunction is substantial 12 months after TAVR and are associated with reduced survival. Impaired mFS and the combination of abnormal LVEF or GLS independently predicted all-cause mortality beyond 12 months after TAVR.

Identification of wild-type transthyretin cardiac amyloidosis in patients with carpal tunnel syndrome surgery (CACTuS).

AIMS: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is an infiltrative cardiomyopathy with a poor prognosis. The condition is associated with carpal tunnel syndrome (CTS), which often precedes the ATTRwt diagnosis by several years. The aim of the study was (i) to screen patients with a recent history of CTS for ATTRwt using red flags, (ii) to determine whether patients with screened ATTRwt had less advanced disease compared with patients with clinical ATTRwt, and (iii) to assess the sensitivity and specificity of known red flags in ATTRwt. METHODS AND RESULTS: Patients aged ≥60 years at the time of CTS surgery were invited for screening. Red flags were defined as elevated biomarker levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) or cardiac troponin, an electrocardiogram pattern associated with ATTRwt, left ventricular hypertrophy (LVH), and impaired longitudinal strain with apical sparring. All patients with a red flag were referred for a diagnostic scintigraphy. Patients with ATTRwt diagnosed by screening were compared with patients with clinical ATTRwt (n = 51) matched by age, gender, and CTS surgery. Among the 120 enrolled subjects (mean age 74.5 years, 90% male), the suspicion of ATTR was raised in 67 (55.8%), and 10 (8.3%) were diagnosed with ATTRwt. Patients identified with ATTRwt were predominantly asymptomatic and had mildly elevated NT-proBNP, mildly increased LVH, preserved left ventricular ejection fraction, and systolic longitudinal function, which differed significantly from clinical ATTRwt controls (P < 0.001). CONCLUSIONS: The study found an ATTRwt prevalence of 8.3% in a population of age and gender-selected patients with a recent history of CTS. The identified patients with ATTRwt had less structural and functional cardiac involvement than clinical ATTRwt controls.

Clinical presentation and cardiac imaging findings in patient cases of perimyocarditis and pericarditis with a temporal association to SARS-CoV-2 vaccination.

Aims: We aimed to investigate and present cases of perimyocarditis and pericarditis verified by cardiovascular resonance (CMR) imaging in patients with a strong temporal association to SARS-CoV-2 vaccination. We sought to describe the clinical presentation including coronary artery angiography, CMR, transthoracic echocardiography, blood samples, electrocardiography, and symptoms. Methods: We included 10 patients admitted with chest pain shortly after vaccination for SARS-CoV-2, who were diagnosed with pericarditis or perimyocarditis by CMR. We reviewed the CMR, echocardiography, electrocardiography, blood samples, coronary artery angiography, vital signs and medical history. The updated Lake Louise Criteria were used to determine the diagnosis by CMR. Results: Eight patients had perimyocarditis and two patients had pericarditis. The mean age was 22 ± 5 years (range 16 to 31 years), 90% were male. The median time from vaccination to hospital admission was 4 days (range 2 to 28 days). Admissions were seen after vaccination with three different SARS-CoV-2 vaccine manufacturers. Nine Patients had ST-elevation on the initial electrocardiography. Peak troponins varied from 357 to 23,547 ng/l, with a median of 4,304 ng/l. Two patients had an LVEF <50% on echocardiography and four patients had left ventricular global longitudinal strain values <18%. CMR revealed preserved left ventricular ejection fraction (LVEF), although one patient had decreased LVEF on CMR. The T1 and T2 mapping values were increased in all patients. Of the 8 patients with perimyocarditis, all patients had signs of myocardial injury in the lateral segments of the left ventricle. Conclusions: This case series of 10 patients supports the emerging evidence of an association between vaccination for SARS-CoV-2 and perimyocarditis and pericarditis, especially in young males. The temporal association was seen after vaccines from three different manufacturers. Imaging data from echocardiography and CMR displayed normal to mildly impaired cardiac function, usually with a mild disease course.

Incidence and predictors of worsening heart failure in patients with wild-type transthyretin cardiac amyloidosis.

BACKGROUND: Prognostic markers of survival have been identified in wild-type transthyretin amyloidosis (ATTRwt), but limited data exist with respect to hospitalizations with worsening heart failure (WHF). Predictive markers of WHF have yet to be identified. METHODS: From April 2017 to February 2021, 104 patients with ATTRwt were diagnosed and prospectively followed from the time of diagnosis to the time of death or the censoring date of 1 February 2021. Baseline patient characteristics, biomarkers, and advanced echocardiography were used to predict hospitalization with WHF. RESULTS: During the median follow-up period of 23 months, 51% of patients were hospitalized due to WHF. Seventy-three per cent of patients with WHF were admitted at least twice. Patients with WHF during the first year had significantly poorer survival (P < 0.001). Independent predictors of WHF during follow-up were pacemaker implantation prior to diagnosis (PMI, P = 0.037) and right atrial volume index (RAVi, P = 0.008). Patients with PMI had a higher left ventricular mass index and poorer left ventricular and right ventricular systolic function indicating a more advanced stage of amyloid disease. CONCLUSIONS: A high incidence and recurrence of hospital admissions with WHF were demonstrated in contemporary patients with ATTRwt, which was associated with reduced survival. Patients with pacemaker devices prior to ATTRwt diagnosis experienced more frequent hospitalizations with WHF. PMI and right atrial enlargement were identified as independent predictors of WHF during follow-up.

Cardiac Performance and Cardiopulmonary Fitness After Infection With SARS-CoV-2.

Aims: Persistent cardiac symptoms are an increasingly reported phenomenon following COVID-19. However, the underlying cause of cardiac symptoms is unknown. This study aimed to identify the underlying causes, if any, of these symptoms 1 year following acute COVID-19 infection. Methods and Results: 22 individuals with persistent cardiac symptoms were prospectively investigated using echocardiography, cardiovascular magnetic resonance (CMR), 6-min walking test, cardio-pulmonary exercise testing and electrocardiography. A median of 382 days (IQR 368, 442) passed between diagnosis of COVID-19 and investigation. As a cohort their echocardiography, CMR, 6-min walking test and exercise testing results were within the normal ranges. There were no differences in left ventricular ejection fraction (61.45 ± 6.59 %), global longitudinal strain (19.80 ± 3.12 %) or tricuspid annular plane systolic excursion (24.96 ± 5.55 mm) as measured by echocardiography compared to a healthy control group. VO2 max (2045.00 ± 658.40 ml/min), % expected VO2 max (114.80 ± 23.08 %) and 6-minute distance walked (608.90 ± 54.51 m) exceeded that expected for the patient cohort, whilst Troponin I (5.59 ± 6.59 ng/l) and Nt-proBNP (88.18 ± 54.27 ng/l) were normal. Conclusion: Among a cohort of 22 patients with self-reported persistent cardiac symptoms, we identified no underlying cardiac disease or reduced cardiopulmonary fitness 1 year following COVID-19.