En mann i 60-årene med dyspné og systolisk bilyd etter hjerteinfarkt.

Background: Ventricular septal rupture (VSR) following acute myocardial infarction is rare in the modern revascularisation era. Nevertheless, clinical awareness is paramount, as presentation may vary. Case presentation: A middle-aged male with no history of cardiovascular disease developed progressive heart failure symptoms while travelling abroad. Initial workup revealed a prominent systolic murmur, but findings were inconsistent with acute coronary syndrome. Transthoracic echocardiogram showed a small hypokinetic area in the basal septum, preserved left ventricular function and no significant valvulopathy. Despite the absence of chest pain, an invasive angiography revealed occlusion of a septal branch emerging from the left anterior descending artery, otherwise patent coronary arteries. Despite administration of diuretics, the patient remained symptomatic and presented two months later to his primary care provider with a persisting systolic murmur. He was subsequently referred to the outpatient cardiology clinic where echocardiography revealed a large VSR involving the basal anteroseptum of the left ventricle with a significant left-to-right shunt. After accurate radiological and haemodynamic assessment of the defect, he successfully underwent elective surgical repair. Interpretation: Although traditionally associated with large transmural myocardial infarctions, VSR may arise also from minor, subclinical events. A new-onset murmur is a valuable hint for the alert clinician.

Diagnostics, treatment and outcomes of cardiac sarcoidosis in a Norwegian cohort.

BACKGROUND: Evidence-based guidelines for cardiac sarcoidosis (CS) regarding use of second- and third-line agents, treatment duration, surveillance and prognostic factors are lacking. OBJECTIVE: To analyze the clinical presentation, diagnostics, treatment, monitoring and clinical outcomes in a Norwegian cohort. METHODS: Using discharge diagnoses between 2017 through 2020 from a large tertiary center, we identified 52 patients with CS. We performed a systematic chart review following a pre-specified checklist. The primary outcome of major cardiovascular events (MACE) was defined as a composite of cardiovascular hospitalization, defibrillator therapy, cardiac transplantation, or death. RESULTS: 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed pathological tracer uptake in 35/36 (97%) of immunosuppression-naïve patients. Immunosuppressive treatment was administered to 49/52 patients (94%) for a median of 43 (IQR 34) months; 69% were treated with second-line (methotrexate, azathioprine, mycophenolate mofetil) and 25% with third-line (rituximab, infliximab) agents, respectively. Rituximab reduced inflammation as assessed by interval FDG-PET imaging and was overall well tolerated. Median duration to first MACE was 6 (IQR 10) months and 17/23 patients (74%) experienced a MACE within 12 months from CS diagnosis. No mortality was recorded and 20% achieved full remission. Age below the median of 53 years at time of diagnosis was associated with an increased risk of a MACE. CONCLUSION: Long-term immunosuppression including a liberal use of non-steroidal agents, appeared essential in treating CS. Although the burden of cardiovascular events was substantial, the survival was excellent in this contemporary cohort. Prospective randomized studies are urgently needed to define the best therapy for these patients.

Invasive haemodynamics at rest and exercise in cardiac amyloidosis.

AIMS: Our aim was to investigate haemodynamics at rest and during exercise in patients with transthyretin cardiomyopathy (ATTR-CM) in light of the 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines on pulmonary hypertension (PH). METHODS AND RESULTS: We performed right heart catheterization (RHC) in 57 subjects with ATTR-CM. The proportion of patients with PH was 77% according to the 2022 guidelines versus 47% when applying the 2015 guidelines. Isolated post-capillary PH and combined pre- and post-capillary PH were most prevalent. Thirty-six patients underwent a supine bicycle cardiopulmonary exercise test during RHC. Exercise-induced PH was defined as an increase in mean pulmonary arterial pressure from rest to exercise per increase in cardiac output (ΔmPAP/ΔCO) of > 3 mmHg/L/min. An increase in pulmonary arterial wedge pressure per change in cardiac output (ΔPAWP/ΔCO) from rest to exercise >2 mmHg/L/min was considered suggestive of post-capillary exercise-induced PH. All but two patients who exercised during RHC developed exercise-induced PH. The median ΔmPAP/ΔCO was 7.2 mmHg/L/min and ΔPAWP/ΔCO was 5.1 mmHg/L/min. The median ΔRAP/ΔCO was 3.6 mmHg/L/min and ΔRAP/ΔPAWP was 0.6 mmHg/L/min. CONCLUSIONS: Most patients with ATTR-CM have isolated post-capillary or combined pre- and post-capillary PH at rest, and almost all patients develop exercise-induced PH with a large post-capillary component. There was a pronounced, but balanced increase in atrial pressures on exercise.

Rates of Second Tumor, Metastasis, and Death From Cutaneous Squamous Cell Carcinoma in Patients With and Without Transplant-Associated Immunosuppression.

Importance: Cutaneous squamous cell carcinoma (cSCC) may occur with multiple primary tumors, metastasize, and cause death both in immunocompetent and immunosuppressed patients. Objective: To study the rates of second cSCC, metastasis, and death from cSCC in patients with and without organ transplant-associated immunosuppressive treatment. Design, Setting, and Participants: This population-based, nationwide cohort study used Cancer Registry of Norway data from 47 992 individuals diagnosed with cSCC at 18 years or older between January 1, 1968, and December 31, 2020. Data were analyzed between November 24, 2021, and November 15, 2022. Exposures: Receipt of a solid organ transplant at Oslo University Hospital between 1968 and 2012 followed by long-term immunosuppressive treatment. Main Outcomes and Measures: Absolute rates of second cSCC, metastasis, and death from cSCC were calculated per 1000 person-years with 95% CIs. Hazard ratios (HRs) estimated using Cox proportional hazard regression were adjusted for age, sex, and year of first cSCC diagnosis. Results: The study cohort comprised 1208 organ transplant recipients (OTRs) (median age, 66 years [range, 27-89 years]; 882 men [73.0%] and 326 women [27.0%]) and 46 784 non-OTRs (median age, 79 years [range, 18-106 years]; 25 406 men [54.3%] and 21 378 women [45.7%]). The rate of a second cSCC per 1000 person-years was 30.9 (95% CI, 30.2-31.6) in non-OTRs and 250.6 (95% CI, 232.2-270.1) in OTRs, with OTRs having a 4.3-fold increased rate in the adjusted analysis. The metastasis rate per 1000 person-years was 2.8 (95% CI, 2.6-3.0) in non-OTRs and 4.8 (95% CI, 3.4-6.7) in OTRs, with OTRs having a 1.5-fold increased rate in the adjusted analysis. A total of 30 451 deaths were observed, of which 29 895 (98.2%) were from causes other than cSCC. Death from cSCC was observed in 516 non-OTRs (1.1%) and 40 OTRs (3.3%). The rate of death from cSCC per 1000 person-years was 1.7 (95% CI, 1.5-1.8) in non-OTRs and 5.4 (95% CI, 3.9-7.4) in OTRs, with OTRs having a 5.5-fold increased rate in the adjusted analysis. Conclusions and Relevance: In this cohort study, OTRs with cSCC had significantly higher rates of second cSCC, metastasis, and death from cSCC than non-OTRs with cSCC, although most patients with cSCC in both groups died from causes other than cSCC. These findings are relevant for the planning of follow-up of patients with cSCC and for skin cancer services.

A man in his seventies with fatigue and renal failure. / En mann i 70-årene med utmattelse og nyresvikt.

A man in his seventies underwent routine heart examinations as part of workup for kidney transplantation. Unexpected findings led to more extensive investigations and revealed two rare systemic diseases as causes of his heart failure.

Bone scintigraphy reduces the need for biopsy in suspected cardiac amyloidosis. / Skjelettscintigrafi reduserer behovet for biopsi ved mistanke om kardial amyloidose.

The gold standard to diagnose suspected cardiac amyloidosis is myocardial biopsy. In recent years, bone scintigraphy has partly replaced myocardial biopsy.

Recurrent pericarditis. / Residiverende perikarditt.

Pericarditis is an important differential diagnosis in patients with chest pain. The two most common causes in the developed world are idiopathic pericarditis and inflammation following cardiac surgery or myocardial infarction. Recurrence of pericarditis affects up to 30 % of patients, half of whom experience multiple episodes, and approximately 10 % develop steroid-dependent and colchicine-refractory pericarditis. Recurrence is due to autoinflammatory processes in the pericardium. Advanced diagnostic imaging and treatment with colchicine and interleukin-1 inhibitors has helped reduce morbidity considerably in recent years. In this clinical review, we summarise up-to-date knowledge about the diagnostic evaluation and treatment of patients with recurrent primary pericarditis.

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.

First Norwegian case of hereditary ATTR amyloidosis with a novel transthyretin variant.

An earlier healthy 64-year-old man with previous surgery for bilateral carpal tunnel syndrome (CTS) in his 50s, presented with dyspnoea on exertion. Cardiac amyloidosis was suspected due to "red flag" signs and symptoms. Further investigations with scintigraphy and genetic testing confirmed the diagnosis of hereditary ATTR variant (ATTRv) amyloidosis. This is the first case report of ATTRv amyloidosis in a patient of Norwegian origin and is caused by the mutation E54A (p.E74A) in the transthyretin (TTR) gene. This mutation is previously not reported in international databases. Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease with a poor prognosis. Early recognition remains essential to afford the best treatment efficacy.

Pulmonary endarterectomy and balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: Comparison of changes in hemodynamics and functional capacity.

The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). Balloon pulmonary angioplasty (BPA) is an emerging option for inoperable patients. Comparisons of the hemodynamic and functional outcome between these treatments are scarce. In this single-center observational cohort study, we compared hemodynamics by right heart catheterization and peak oxygen consumption before and 5 months (±14 days) after either PEA or BPA. Comprehensive evaluation and selection for PEA or BPA was performed by an expert CTEPH team. Fourty-two and fourty consecutive patients were treated with PEA or BPA, respectively. Demographics were similar between groups. Both PEA and BPA significantly reduced mean pulmonary artery pressure (from 46 ± 11 mmHg at baseline to 28 ± 13 mmHg at follow-up; p < 0.001 and from 43 ± 12 mmHg to 31 ± 9 mmHg; p < 0.001) and pulmonary vascular resistance (from 686 ± 347 dyn s cm-5 at baseline to 281 ± 197 dyn s cm-5 at follow-up; p < 0.001 and from 544 ± 322 dyn s cm-5 to 338 ± 180 dyn s cm-5; p < 0.001), with significantly lower reductions for both parameters in the former group. However, cardiopulmonary exercise testing revealed no significant between group differences in exercise capacity. Diffusion capacity for carbon monoxide at baseline was the only follow-up predictor for peak VO2. In our study, PEA reduced pulmonary pressures more than BPA did, but similar improvements were observed for exercise capacity. Thus, while long term data after BPA is lacking, BPA treated CTEPH patients can expect physical gains in line with PEA.

Can mechanical circulatory support be an effective treatment for HFpEF patients?

Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence and represents approximately 50% of all heart failure (HF) patients. Patients with this complex clinical scenario, characterized by high filling pressures, and reduced cardiac output (CO) associated with progressive multi-organ involvement, have so far not experienced any significant improvement in quality of life or survival with traditional HF treatment. Left ventricular assist devices (LVAD) have offered a new treatment alternative in terminal heart failure patients with reduced ejection fraction (HFrEF), providing a unique combination of significant pressure and volume unloading together with an increase in CO. The small left ventricular cavity in HFpEF patients challenges left-sided pressure unloading, and new anatomical entry points need to be explored for mechanical pressure and volume unloading. Optimized and pressure/volume-adjusted mechanical circulatory support (MCS) devices for HFrEF patients may conceivably be customized for HFpEF anatomy and hemodynamics. We have developed a long-term MCS device for HFpEF patients with atrial unloading in a pulsed algorithm, leading to a significant reduction of filling pressure, maintenance of pulse pressure, and increase in CO demonstrated in animal testing. In this article, we will discuss HFpEF pathology, hemodynamics, and the principles behind our novel MCS device that may improve symptoms and prognosis in HFpEF patients. Data from mock-loop hemolysis studies, acute, and chronic animal studies will be presented.

A case report of giant cell myocarditis complicated by severe heart failure: the value of early endomyocardial biopsy and mechanical circulatory support.

Background: Giant cell myocarditis (GCM) is a rare, probably underdiagnosed and potentially fatal disease in young and middle-aged patients. Disease progression is often rapid, and life-threatening arrhythmias and cardiogenic shock due to progressive left ventricular failure are among the most feared complications. Although cardiac biomarkers and multimodality imaging are used as initial diagnostic tests in most patients, endomyocardial biopsy (EMB) is often required for a definitive diagnosis. However, there are still gaps in our knowledge in terms of the etiology, early diagnosis, management and prognosis of GCM. Case Description: We present the case of a male patient in his early 50s admitted to Haukeland University Hospital with fulminant GCM. He had no significant medical history in the past apart from hypertension, and presented to hospital in cardiogenic shock after a few weeks of progressive shortness of breath. Rapid initiation of methylprednisolone had an immediate effect on reducing myocardial inflammation, and sustained treatment with a combination of immunosuppressive agents along with optimal heart failure medications led to complete recovery of the heart function and clinical remission over several years. The case study highlights the urgency of an early EMB, access to mechanical circulatory support (MCS) and the efficacy of immunosuppressive treatment and optimal medical management for heart failure. Finally, our review of the literature also provides an updated guidance on the contemporary management of GCM patients. Conclusions: Accurate and early diagnosis with EMB in patients with GCM are crucial for better outcomes. Rapid initiation of methylprednisolone reduces myocardial inflammation and the risk of death. Sustained treatment with a combination of immunosuppressive agents together with optimal heart failure medications are essential for myocardial recovery and long-term stabilization. The use of MCS is the cornerstone in the management of GCM with a clear survival benefit.

Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension.

Introduction: Systemic sclerosis (SSc) is a heterogenous disorder that appears to result from interplay between vascular pathologies, tissue fibrosis and immune processes, with evidence for deregulation of chemokines, which normally control immune trafficking. We recently identified altered levels of chemokine CCL21 in SSc associated pulmonary arterial hypertension (PAH). Here, we aimed to define target organ expression and biomarker characteristics of CCL21. Materials and methods: To investigate target organ expression of CCL21, we performed immunohistochemistry (IHC) on explanted lung tissues from SSc-PAH patients. We assessed serum levels of CCL21 by ELISA and Luminex in two well-characterized SSc cohorts from Oslo (OUH, n=552) and Zurich (n=93) University hospitals and in 168 healthy controls. For detection of anti-CCl21 antibodies, we performed protein array analysis applying serum samples from SSc patients (n=300) and healthy controls. To characterize circulating CCL21 in SSc, we applied immunoprecipitation (IP) with antibodies detecting both full length and tailless and a custom-made antibody detecting only the C-terminal of CCL21. IP products were analyzed by SDS-PAGE/western blot and Mass spectrometry (MS). Results: By IHC, we found that CCL21 was mainly expressed in the airway epithelial cells of SSc patients with PAH. In the analysis of serum levels of CCL21 we found weak correlation between Luminex and ELISA (r=0.515, p<0.001). Serum levels of anti-CCL21 antibodies were higher in SSc patients than in healthy controls (p<0.001), but only 5% of the SSc population were positive for anti-CCL21 antibodies in SSc, and we found no correlation between anti-CCl21 and serum levels of CCL21. By MS, we only identified peptides located within amino acid (aa) 23-102 of CCL21, indicating that CCL21 in SSc circulate as a truncated protein without the C-terminal tail. Conclusion: This study demonstrates expression of CCL21 in epithelial lung tissue from SSc patients with PAH, and indicate that CCL21 in SSc circulates as a truncated protein. We extend previous observations indicating biomarker potential of CCL21, but find that Luminex is not suitable as platform for biomarker analyses. Finally, in vivo generated anti-CCL21 antibodies exist in SSc, but do not appear to modify serum CCL21 levels in patients with SSc-PAH.

Iron homeostasis in heart transplant recipients randomized to ferric derisomaltose or placebo.

INTRODUCTION: The randomized IronIC trial evaluated the effect of intravenous ferric derisomaltose on physical capacity in iron-deficient, maintenance heart transplant (HTx) recipients. Iron deficiency was defined as in heart failure with high cut-points for ferritin to compensate for inflammation. However, intravenous iron did not improve physical capacity except in patients with ferritin <30 µg/L. We aimed to explore determinants of iron status in the 102 IronIC participants to better define iron deficiency in the HTx population. METHODS: We assessed key governors of iron homeostasis, such as hepcidin, soluble transferrin receptor (sTfR), and interleukin-6 (IL-6). We also measured growth factors and inflammatory markers with relevance for iron metabolism. The results were compared to those of 21 healthy controls. RESULTS: Hepcidin did not differ between HTx recipients and controls, even though markers of inflammation were modestly elevated. However, HTx recipients with ferritin <30 µg/L or sTfR above the reference range had significantly reduced hepcidin levels suggestive of true iron deficiency. In these patients, intravenous iron improved peak oxygen uptake. Hepcidin correlated positively with ferritin and negatively with sTfR. CONCLUSION: HTx recipients with iron deficiency as defined in heart failure do not have elevated hepcidin levels, although inflammatory markers are modestly increased. The high ferritin cut-offs used in heart failure may not be suitable to define iron deficiency in the HTx population. We suggest that hepcidin and sTfR should be measured to identify patients with true iron deficiency, who might benefit from treatment with intravenous iron.

Prevalence, characteristics, and mortality of patients with transthyretin amyloid cardiomyopathy in the Nordic countries.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using multiple national health registers in Denmark, Finland, Norway, and Sweden. METHODS AND RESULTS: Transthyretin amyloid cardiomyopathy patients were identified during 2008-2018 using a combination of diagnosis codes for amyloidosis and heart disease and were matched to patients with non-ATTR heart failure (HF). An identical study design was used in each country to facilitate comparison and aggregation of results. A total of 1930 ATTR-CM patients were identified from national health registers in the four countries. In 2018, prevalence of ATTR-CM per 100 000 inhabitants ranged from 1.4 in Denmark to 5.0 in Sweden; a steep increase over time was observed in Sweden and Norway. Median survival from diagnosis was 30 months for ATTR-CM patients and 67 months for matched HF patients. Survival was significantly lower for female than for male ATTR-CM patients (median survival: 22 and 36 months), while no significant difference was observed in the HF cohort. CONCLUSIONS: This study provides the first nationwide estimates of the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using identical study design across several countries. Findings corroborate previous case series showing high mortality in ATTR-CM, two-fold higher than for other HF patients and higher in women than men, highlighting the need for more precise and early diagnosis to reduce the disease burden.

Healthcare resource use of patients with transthyretin amyloid cardiomyopathy.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is the cardiac manifestation of transthyretin amyloidosis (ATTR). The aim of this study was to estimate healthcare resource use for ATTR-CM patients compared with heart failure (HF) patients, in Denmark, Finland, Norway, and Sweden. METHODS AND RESULTS: Data from nationwide healthcare registers in the four countries were used. ATTR-CM patients were defined as individuals diagnosed with amyloidosis and cardiomyopathy or HF between 2008 and 2018. Patients in the ATTR-CM cohort were matched to patients with HF but without ATTR-CM diagnosis. Resource use included number of visits to specialty outpatient and inpatient hospital care. A total of 1831 ATTR-CM and 1831 HF patients were included in the analysis. The mean number of hospital-based healthcare contacts increased in both the ATTR-CM and HF cohort during 3 years pre-diagnosis and was consistently higher for the ATTR-CM cohort compared with the HF cohort, with 6.1 [CI: 5.9-6.3] vs. 3.2 [CI: 3.1-3.3] outpatient visits and 1.03 [CI: 0.96-1.1] vs. 0.7 [CI: 0.7-0.8] hospitalizations. In the first year following diagnosis, patients with ATTR-CM continued to visit outpatient care (10.2 [CI: 10.1, 10.4] vs. 5.7 [CI: 5.6, 5.9]) and were admitted to hospital more frequently (3.3 [CI: 3.2, 3.4] vs. 2.5 [CI: 2.5, 2.6]) than HF patients. CONCLUSIONS: Transthyretin amyloid cardiomyopathy imposes a high burden on healthcare systems with twice as many outpatient specialist visits and 50% more hospitalizations in the year after diagnosis compared with HF patients without ATTR-CM. Studies to investigate if earlier diagnosis and treatment of ATTR-CM may lower resource use are warranted.

Diastolic Dysfunction Is Unmasked on Exercise in Patients With Asymptomatic, Severe Aortic Stenosis: An Invasive Hemodynamic Study.

BACKGROUND: Optimal timing of aortic valve replacement remains difficult in patients with asymptomatic, severe aortic stenosis (AS). More accurate diagnostic methods are warranted for the detection of subtle ventricular impairment. We aimed to evaluate diastolic function in asymptomatic patients with severe AS. METHODS: In this cross-sectional study, patients with asymptomatic, severe AS were evaluated with right heart catheterization at rest and during moderate exercise. The patients also underwent cardiopulmonary exercise testing to objectify functional capacity and confirm the absence of symptoms. RESULTS: Between February 2019 and May 2021, we included 50 patients aged 70±12 years. The patients had severe AS with peak velocity 4.4±0.4 m/s, mean gradient 46±9 mm Hg, and an indexed valve area of 0.47±0.08 cm2 at rest. All patients were asymptomatic and had normal left ventricular ejection fraction. Five patients had postcapillary pulmonary hypertension at rest. During exercise, 44 patients (88%) had an increase in the mean pulmonary artery pressure per increase in cardiac output of >3 mm Hg/L per minute, of whom 93% had a concomitant increase in the pulmonary artery wedge pressure per increase in cardiac output >2 mm Hg/L per minute, suggesting exercise-induced pulmonary hypertension due to left heart disease. Female gender and increasing age were associated with a higher increase in the pulmonary artery wedge pressure per increase in cardiac output ratio. The catheterization was well tolerated, and there were no adverse events. CONCLUSIONS: A large proportion of asymptomatic patients with severe, degenerative AS have exercise-induced postcapillary pulmonary hypertension.

Nationwide prevalence and characteristics of transthyretin amyloid cardiomyopathy in Sweden.

OBJECTIVE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressive and fatal condition caused by deposition of transthyretin amyloid fibrils in the heart. This study aims to identify all patients diagnosed with ATTR-CM in Sweden, estimate the prevalence of ATTR-CM, describe patient characteristics and mortality, assess the importance of early symptoms (red flags) for identification of ATTR-CM, and compare with patients with heart failure (HF). METHODS: This retrospective study combined multiple national health registers covering all specialist visits and prescriptions for the entire population of Sweden. Between January 2008 and December 2018, patients with ATTR-CM were identified retrospectively based on a combination of diagnosis codes and compared with matched, all-cause non-ATTR HF patients. RESULTS: Overall, a total of 994 patients diagnosed with ATTR-CM were identified, with an average age at diagnosis of 73 years, and 30% of whom were female. The prevalence of diagnosed ATTR-CM cases in 2018 was 5.0 per 100 000. The median survival from diagnosis was 37.6 months (CI 33.8 to 43.8), with a lower median survival in women (27.9 months, CI 23.3 to 33.8) compared with men (43.5 months, CI 37.6 to 49.6). Patients with ATTR-CM demonstrated reduced survival compared with patients with HF (p<0.001). Compared with patients with HF, clinical identification of carpal tunnel syndrome, spinal stenosis, and atrioventricular and left bundle branch block can facilitate earlier diagnosis of ATTR-CM. CONCLUSIONS: This study provides the first nationwide estimates of ATTR-CM prevalence and risk factors. The results reinforce the severity of the disease and the importance of earlier diagnosis, especially for female patients, in order to allow effective treatment and prevention of disease progression.