Changes in Exercise Tolerance over Time in Patients with Transthyretin Amyloidosis Cardiomyopathy Treated with Tafamidis.

Tafamidis improves the prognosis of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM). Additionally, it delays the decline in exercise tolerance, as observed in the six-minute walking test. However, the changes in cardiopulmonary function over time based on cardiopulmonary exercise tests are unclear. Thus, this preliminary study investigated the changes in exercise tolerance after one year of tafamidis treatment using cardiopulmonary exercise testing. Eight patients with ATTR-CM (average age: 77 years; male: n = 7) underwent cardiopulmonary exercise testing at baseline and after one year of tafamidis treatment. All eight patients completed a one-year follow-up. At baseline, the anaerobic threshold oxygen uptake (AT VO2: 10.9 ± 1.5) and peak VO2 (14.3 ± 3.0 mL/kg/minute) indicated relatively favorable exercise capacity; however, the minute ventilation/carbon dioxide production (VE/VCO2 slope), which indicates effective ventilation, showed poor performance (33.7 ± 12.8). One year after tafamidis treatment, frailty, as assessed by the Clinical Frailty Scale, had progressed in seven of eight patients (88%) (P < 0.01), and AT VO2 and peak VO2 were significantly reduced (19.2% and 22.3%, respectively; P < 0.05). The VE/VCO2 slope and peak O2 pulse decreased nonsignificantly by approximately 20% (P = 0.47, and P = 0.16, respectively). Further, the structure of the ventricles and atrium and the left ventricle ejection fraction on echocardiography did not change. Thus, exercise tolerance in patients with ATTR-CM was reduced after one year despite tafamidis administration. Not only ATTR-CM progression, but also frailty progression may influence this decrease in exercise tolerance. A comprehensive approach, including tafamidis administration and cardiac rehabilitation, is required for further improvement in the exercise capacity of patients with ATTR-CM.

Reduction of left ventricular pressure gradient due to cibenzoline therapy in a 16-year-old girl with hypertrophic obstructive cardiomyopathy.

A 13-year-old girl was referred for closer examination of electrocardiographic abnormalities. She had a Levine 2/6 systolic murmur (SM) and a fourth heart sound. Electrocardiography findings showed poor R progression from V1 to V4 and negative T waves in the II, III, and aVF leads. Approximately 3.2 years later, her SM increased to Levine 3-4/6. Echocardiography indicated mitral regurgitation and left ventricular pressure gradient (LVPG) of 18.5 mmHg, together with a notch on the systolic wave in the apexcardiogram. We concluded that the electrocardiographic abnormalities were caused by hypertrophic cardiomyopathy. Approximately 6 months later, her SM further increased to Levine 4-5/6, and the voltage on the electrocardiogram increased. In carotid pulse tracing, steep upstroke and deflated percussion wave due to mitral regurgitation were noted. The LVPG was approximately 102 mmHg, and systolic anterior movement was confirmed. After the oral administration of 200 mg of cibenzoline, the LVPG decreased to approximately 48 mmHg. Subsequently, 300 mg/day of cibenzoline was administered. The LVPG further decreased, and her symptoms improved. Learning objectives: Clinical symptoms and left ventricular pressure gradient decrease can be ameliorated by cibenzoline therapy in patients with hypertrophic obstructive cardiomyopathy. This finding applies not only to adult patients but also to teen-aged patients.

Changes of left ventricular remodeling due to increased afterload in patients with essential hypertension.

BACKGROUND: It is unclear whether afterload mismatch occurs during the initial stage of essential hypertension (EHT). Additionally, critical left ventricular hypertrophy (LVH) between preserved and reduced systolic functions in hypertension is also unclear. Thus, we aimed to clarify these points. METHODS: Forty-five normal control subjects (NCS) and 140 EHT patients participated. EHT patients were subdivided into three groups: group I, without LVH (n = 37); group II, with LVH (n = 80); and group III, with LVH and LV heart failure (LVHF) (n = 23). Routine electrocardiographic and echocardiographic parameters, V5R/V6R ratio, relative wall thickness (RWT), LV mass (LVM) index, and peak systolic wall stress (PSWS) were measured. RESULTS: In group I, LV systolic functions were preserved despite the increase of PSWS. In group II, LVH advanced, but LV systolic functions remained normal. A negative T-wave was observed in 69% of group II and 100% of group III. A significant correlation between RWT and LVM index was seen in NCS and groups I and II (r2 = 0.545, P < 0.0001) but not in group III. Afterload mismatch occurred in group III due to the decrease in V5R/V6R ratio, the increase of LV end-diastolic dimension, and the LV systolic dysfunctions, which are caused by exhaustion of preload reserve. The boundary of the LVM index between groups II and III was approximately 180 g/m2. CONCLUSION: Afterload mismatch did not occur in group I, but it was observed in group III due to the exhaustion of preload reserve.

Impact of hyperuricemia on coronary blood flow and in-hospital mortality in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Although serum uric acid (UA) is considered as a risk factor for cardiovascular disease, few data exist regarding the relationship between hyperuricemia, coronary blood flow, and subsequent outcome in patients with acute myocardial infarction (AMI). The purpose of our study is to assess whether hyperuricemia is associated with suboptimal coronary flow and increased risk of mortality in patients with AMI after percutaneous coronary intervention (PCI). METHODS: Using the Rural AMI registry data, 989 consecutive patients with AMI who underwent emergent PCI and had UA measurement at admission were analyzed. We defined hyperuricemia as serum UA ≥7.0 mg/dL in men and ≥ 6.0 mg/dL in women. The primary endpoint was suboptimal coronary flow, defined as post PCI Thrombosis In Myocardial Infarction flow grade ≤ 2. The secondary outcome was in-hospital mortality. RESULTS: Hyperuricemia was found in 249 (25.2%) patients. Patients with hyperuricemia were more often complicated with cardiogenic shock compared with those without (16.9% vs. 7.4%, p < 0.001). In addition, the median high-sensitivity C-reactive protein was significantly higher in patients with hyperuricemia (0.18 mg/dL; IQR, 0.09-0.71 mg/dL) than in those without (0.14 mg/dL; IQR, 0.07-0.41 mg/dL, p < 0.05). Under these conditions, the prevalence of suboptimal coronary flow after PCI (17.3% vs. 10.1%, p < 0.05) and in-hospital mortality (10.8% vs. 3.6%, p < 0.001) were significantly higher in patients with hyperuricemia compared with those without. Multivariable logistic regression analysis revealed that hyperuricemia was significantly associated with suboptimal coronary flow [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.49; p < 0.05] and in-hospital mortality (OR, 2.08; 95% CI, 1.05-4.12; p < 0.05). CONCLUSIONS: Assessment of serum UA upon admission provides useful information for predicting suboptimal coronary flow and in-hospital mortality in patients with AMI undergoing PCI.

Effect of 15-mg Edoxaban on Clinical Outcomes in 3 Age Strata in Older Patients With Atrial Fibrillation: A Prespecified Subanalysis of the ELDERCARE-AF Randomized Clinical Trial.

Importance: Long-term use of oral anticoagulants (OACs) is necessary for stroke prevention in patients with atrial fibrillation (AF). The effectiveness and safety of OACs in extremely older patients (ie, aged 80 years or older) with AF and at high risk of bleeding needs to be elucidated. Objective: To examine the effects of very low-dose edoxaban (15 mg) vs placebo across 3 age strata (80-84 years, 85-89 years, and ≥90 years) among patients with AF who were a part of the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial. Design, Setting, and Participants: This prespecified subanalysis of a phase 3, randomized, double-blind, placebo-controlled trial was conducted from August 5, 2016, to December 27, 2019. Patients with AF aged 80 years or older who were not considered candidates for standard-dose OACs were included in the study; reasons these patients could not take standard-dose OACs included low creatinine clearance (<30 mL per minute), low body weight (≤45 kg), history of bleeding from critical organs, continuous use of nonsteroidal anti-inflammatory drugs, or concomitant use of antiplatelet drugs. Eligible patients were recruited randomly from 164 hospitals in Japan and were randomly assigned 1:1 to edoxaban or placebo. Interventions: Edoxaban (15 mg once daily) or placebo. Main Outcomes and Measures: The primary efficacy end point was the composite of stroke or systemic embolism. The primary safety end point was International Society on Thrombosis and Hemostasis-defined major bleeding. Results: A total of 984 patients (mean [SD] age: age group 80-84 years, 82.2 [1.4] years; age group 85-89 years, 86.8 [1.4] years; age group ≥90 years, 92.3 [2.1] years; 565 women [57.4%]) were included in this study. In the placebo group, estimated (SE) event rates for stroke or systemic embolism increased with age and were 3.9% (1.2%) per patient-year in the group aged 80 to 84 years (n = 181), 7.3% (1.7%) per patient-year in the group aged 85 to 89 years (n = 184), and 10.1% (2.5%) per patient-year in the group aged 90 years or older (n = 127). A 15-mg dose of edoxaban consistently decreased the event rates for stroke or systemic embolism with no interaction with age (80-84 years, hazard ratio [HR], 0.41; 95% CI, 0.13-1.31; P = .13; 85-89 years, HR, 0.42; 95% CI, 0.17-0.99; P = .05; ≥90 years, HR, 0.23; 95% CI, 0.08-0.68; P = .008; interaction P = .65). Major bleeding and major or clinically relevant nonmajor bleeding events were numerically higher with edoxaban, but the differences did not reach statistical significance, and there was no interaction with age. There was no difference in the event rate for all-cause death between the edoxaban and placebo groups in all age strata. Conclusions and Relevance: Results of this subanalysis of the ELDERCARE-AF randomized clinical trial revealed that among Japanese patients aged 80 years or older with AF who were not considered candidates for standard OACs, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism consistently across all 3 age strata, including those aged 90 years or older, albeit with a higher but nonstatistically significant incidence of bleeding. Trial Registration: ClinicalTrials.gov Identifier: NCT02801669.

Potentially Life-threatening Arrhythmia Triggered by an Excessive Consumption of Dried Sweet Potato "Hoshi-Imo".

We herein report two cases of potentially life-threatening arrhythmia due to hyperkalemia triggered by the excessive consumption of "Hoshi-Imo" (dried sweet potato). Both patients with chronic renal disease on renin-angiotensin-aldosterone system inhibitors presented at the emergency room with non-specific symptoms. Electrocardiograms revealed potentially life-threatening arrhythmia due to hyperkalemia in both cases: sinus arrest with a ventricular escape rhythm, tall and peaked T waves; and a widened QRS complex in a nearly sine-wave configuration without discernible P wave. Both patients fully recovered after intensive care for hyperkalemia. Physicians should recognize the excessive consumption of "Hoshi-Imo" may lead to the development of life-threatening arrhythmia, especially in patients with risk factors for hyperkalemia.

Impact of cibenzoline treatment on left ventricular remodelling and prognosis in hypertrophic obstructive cardiomyopathy.

AIMS: This study aimed to elucidate the long-term effect of cibenzoline therapy on cardiovascular complications and prognosis in patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS AND RESULTS: Eighty-eight patients with HOCM were treated with cibenzoline (Group A), and 41 patients did not receive cibenzoline (Group B). The changes in left ventricular (LV) remodelling, incidences of cardiovascular complications and deaths, were examined. The mean follow-up period was 15.8 ± 5.6 years in Group A and 17.8 ± 7.2 years in Group B. In Group A, the LV pressure gradient (LVPG) decreased immediately after treatment, and the reduction was maintained throughout the study. In Group B, the LVPG decreased gradually according to the deterioration of LV function. LV reverse remodelling was confirmed in Group A, and LV remodelling advanced in Group B. In Group A, the incidence of each cardiovascular complication was <10%. Only one patient experienced LV heart failure (LVHF). LVHF incidence and atrial fibrillation were higher in Group B than those in Group A (P < 0.0001). The incidence of death was 20.5% in Group A and 90.2% in Group B (P < 0.0001). The most frequent cause of death was sudden cardiac death (SCD) (38.9%) in Group A and LVHF (67.6%) in Group B. The incidence of SCD showed no significant difference between the two groups. The cumulative cardiac survival rate was higher in Group A than that in Group B (P < 0.0001). CONCLUSIONS: Cibenzoline treatment significantly reduced all cardiovascular complications and death due to LVHF and may be a promising treatment in patients with HOCM.

Vanishing Cardiac Tumor by Chemotherapy in a Patient With Diffuse Large B-Cell Lymphoma.

A 70-year-old Japanese man presented with a massive cardiac tumor associated with diffuse large B-cell lymphoma. Standard chemotherapy resulted in complete remission and the cardiac tumor disappeared. (Level of Difficulty: Intermediate.).

Cardiac amyloidosis screening using a relative apical sparing pattern in patients with left ventricular hypertrophy.

BACKGROUND: Cardiac amyloidosis (CA) mimics left ventricular hypertrophy (LVH). It is treatable, but its prognosis is poor. A simple screening tool for CA would be valuable. CA is more precisely diagnosed with echocardiographic deformation parameters (e.g., relative apical sparing pattern [RASP]) than with conventional parameters. We aimed to 1) investigate incremental benefits of echocardiographic deformation parameters over established parameters for CA screening; 2) determine the resultant risk score for CA screening; and 3) externally validate the score in LVH patients. METHODS: We retrospectively studied 295 consecutive non-ischemic LVH patients who underwent detailed diagnostic tests. CA was diagnosed with biopsy or 99mTc-PYP scintigraphy. The base model comprised age (≥65 years [men], ≥70 years [women]), low voltage on the electrocardiogram, and posterior wall thickness ≥ 14 mm in reference to the literature. The incremental benefit of each binarized echocardiographic parameter over the base model was assessed using receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC). RESULTS: Fifty-four (18%) patients had CA. RASP showed the most incremental benefit for CA screening over the base model. After conducting multiple logistic regression analysis for CA screening using four variables (RASP and base model components), a score was determined (range, 0-4 points). The score demonstrated adequate discrimination ability for CA (AUC = 0.86). This result was confirmed in another validation cohort (178 patients, AUC = 0.88). CONCLUSIONS: We developed a score incorporating RASP for CA screening. This score is potentially useful in the risk stratification and management of LVH patients.

Early cardiac rehabilitation for acute decompensated heart failure safely improves physical function (PEARL study): a randomized controlled trial.

BACKGROUND: Improvements in the Short Physical Performance Battery (SPPB) rather than exercise tolerance reportedly led to favorable prognosis in elderly patients with acute decompensated heart failure (ADHF). However, about 50% of heart failure shows heart failure with preserved ejection fraction, safe and effective interventions to improve SPPB for these types remain unclear. In addition, although a standard cardiac rehabilitation (CR) program for heart failure is widely used in Japan, whether this is sufficient to improve SPPB in elderly patients with ADHF remains unclear. AIM: This study aimed to evaluate whether the addition of multidisciplinary physical interventions to the standard CR program would prove effective for improving SPPB among elderly patients with ADHF regardless types of heart failure. DESING: The design of this study was randomized, prospective study. SETTING: Patients admitted to our hospital due to ADHF in Japan. POPULATION: Elderly patients with ADHF between March 2019 and March 2020 were randomized to two groups, an Intervention group and a Control group. METHODS: The Control group performed standard CR. The Intervention group received balance training and resistance training and used a cycling ergometer in addition to the standard CR program. The primary outcome was the improvement in SPPB after CR. RESULTS: Seventy-five patients with ADHF were divided into the two groups (Intervention group, N.=36; Control group, N.=39). At baseline, both groups showed low physical performance and a high prevalence of frailty. Intervention size effect was an improvement in SPPB score of +2.2 (+3.7±1.1 vs. +1.5±1.7; P<0.001). Of the 3 components of SPPB, both gait speed and timed repeated chair rise were significantly improved in the Intervention group compared to the Control group, with intervention size effect of +0.76 and +0.94, respectively (P<0.001). Subgroup analysis of heart failure with preserved ejection fraction showed significant improvement in SPPB score in the Intervention group compared to the Control group (P<0.001). No adverse events were observed during the study period. CONCLUSIONS: A multi-faceted intervention in addition to standard CR improved physical performance among elderly patients with ADHF regardless types of heart failure. CLINICAL REHABILITATION IMPACT: We believe that use of a cycling ergometer and load-specific resistance training provide specific CR for patients with ADHF during acute hospitalization and highlight the need for active intervention.

Comparison of Door-to-Balloon Time and 30-Day Mortality According to Symptom Presentation in Patients With Acute Myocardial Infarction.

Background: We hypothesized that symptom presentation in patients with acute myocardial infarction (AMI) may affect their management and subsequent outcome. Methods and Results: Using Rural AMI Registry data, 1,337 consecutive patients with AMI who underwent percutaneous coronary intervention were analyzed. Typical symptoms were defined as any symptoms of chest pain or pressure due to myocardial ischemia. We considered the specific symptoms of dyspnea, nausea, or vomiting as atypical symptoms. The primary outcome was 30-day mortality. There were 150 (11.2%) and 1,187 (88.8%) patients who presented with atypical and typical symptoms, respectively. Those who presented with atypical symptoms were significantly older (mean [±SD] age 74±12 vs. 68±13 years; P<0.001) and had a higher Killip class (46.7% vs. 21.8%; P<0.001) than patients presenting with typical symptoms. The prevalence of door-to-balloon time of ≤90 min was significantly lower in patients with atypical than typical symptoms (40.0% vs. 66.3%; P<0.001). At 30 days, there were 55 incidents of all-cause death. Multivariate Cox proportional hazards regression analysis revealed that symptom presentation was associated with 30-day mortality (hazard ratio 2.33; 95% confidence interval 1.20-4.38; P<0.05). Conclusions: Atypical symptoms in patients with AMI are less likely to lead to timely reperfusion and are associated with increased risk of 30-day mortality.

Predicting the clinical course in hypertrophic cardiomyopathy using thallium-201 myocardial scintigraphy.

AIMS: This study aimed to evaluate the changes in left ventricular remodelling with time in patients with hypertrophic cardiomyopathy (HCM) using thallium-201 myocardial scintigraphy. METHODS AND RESULTS: Forty-eight patients with HCM participated in the study. The extent score (ES) and a newly devised index termed the 'mean count change' (MCC) were used to evaluate the myocardial perfusion defects. Using the amount of thallium-201 uptake (TU), MCC (%) was calculated using the following formula: (last TU - initial TU)∕initial TU × 100. To confirm the site of the lesion, the left ventricle was divided into five segments: anterior, septal, inferior, lateral, and apex. Cardiovascular complications and deaths were recorded. The mean follow-up period was 8.6 ± 2.0 years. ES increased from 17.4 ± 13.7% to 44.0 ± 22.3% (P < 0.0001). MCC increased from 0% to 12.0 ± 9.0% (P < 0.0001). The apex was the most frequent site of lesion. Twenty-seven patients (56.3%) had experienced left ventricular heart failure (LVHF). Both ES and MCC were greater in patients with LVHF than in those without LVHF. An overlap between the two groups was greater in ES than in MCC. Patients with LVHF had a higher incidence of atrial fibrillation and apoplexy. Nineteen patients (39.6%) died during the study period; 14 died from LVHF, 3 from sudden cardiac death, and 2 from cancer. CONCLUSIONS: Thallium-201 myocardial scintigraphy is useful for detecting the severity of myocardial damage and for confirming the lesion site in patients with HCM. MCC may be superior to ES in the evaluation of these changes with time.

Semiquantitative assessment of the relative apical sparing pattern of longitudinal strain for cardiac amyloidosis identification.

BACKGROUNDS: The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, the visual assessment of RASP is inconsistent, and the quantitative assessment of RASP is time-consuming. This study aimed to compare assessments of RASP for the identification of CA with conventional assessments and investigate their reproducibility and relevance on the assessments. METHODS: Forty patients with biopsy-proven CA were compared with 80 hypertrophied patients matched for mean LV wall thickness. We compared the discriminative abilities of three assessments of RASP to identify CA (visual, quantitative, and semiquantitative). Nine patterns of semiquantitative RASP were investigated; finally, it was defined as "reduction of LS" (≥ -10%) in ≥5 (of 6) basal segments, relative to "preserved LS" (< -15%) in at least one apical segment. RESULTS: The concordance between the two observers for visual RASP was modest (κ = 0.65). On the other hand, the consistency for semiquantitative RASP was perfect (κ = 1.00). The discriminative ability of semiquantitative RASP (area under the curve [AUC]  = 0.74) was significantly better than that of visual RASP (AUC = 0.65) and equivalent to that of binary quantitative RASP. CONCLUSION: Semiquantitative RASP assessment is reproducible and accurately discriminates CA. This simple assessment may help readily refine the risk stratification of patients with diffuse LV hypertrophy.

Features and clinical impact of extra-cardiac lesions with 18F-fluorodeoxyglucose positron emission tomography in patients with suspected cardiac sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic inflammatory disorder and can often affect any other organs beyond the heart. Whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is used to detect not only cardiac but also extra-cardiac involvement of sarcoidosis. However, the features and clinical impact of extra-cardiac lesions have not yet been fully elucidated. Therefore, this study aimed to clarify these using FDG-PET. METHODS AND RESULTS: We enrolled 120 consecutive patients with abnormal findings clinically suggesting cardiac sarcoidosis who underwent whole-body FDG-PET. In this study, a patient with suspected cardiac sarcoidosis was defined as one having both clinically suspected findings and FDG-PET positive cardiac uptake. Subsequently, a total of 36 patients with suspected cardiac sarcoidosis were found and analyzed. Extra-cardiac involvement was detected in 35 lesions of 14 patients (39% per patient). In particular, the extra-cardiac lesions were widely distributed throughout the body, and mediastinal/hilar lymph node involvement was most commonly observed. In most of the patients (93% per patient, 13/14), the extra-cardiac lesions were localized in the regions that were considered more accessible with less risk of complication compared with endomyocardial biopsy (EMB). Based on the FDG-PET findings, 8 patients underwent extra-cardiac biopsy without complication, and its diagnostic sensitivity for histological sarcoidosis was high (75%, 6/8). Moreover, FDG-PET-guided extra-cardiac biopsy could confirm histological sarcoidosis in 4 lesions that EMB failed to prove. CONCLUSIONS: Extra-cardiac involvement in patients with suspected cardiac sarcoidosis was relatively high. FDG-PET-guided extra-cardiac biopsy may be safe and useful for the imaging based diagnosis of cardiac sarcoidosis.

Diagnostic accuracy of stress myocardial computed tomography perfusion imaging to detect myocardial ischemia: a comparison with coronary flow velocity reserve derived from transthoracic Doppler echocardiography.

BACKGROUND: Our aim was to evaluate the ability of adenosine triphosphate (ATP)-stress myocardial computed tomography perfusion (CTP) imaging to detect myocardial ischemia in the left anterior descending artery (LAD) territory, and to compare this method with coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography (TTDE). METHODS: ATP-stress CTP and CFVR were performed in 50 patients with stable angina pectoris. Myocardial ischemia assessed from CTP imaging was defined as qualitative visual perfusion defects and reduced myocardial blood flow (MBF) based on quantitative assessment. A cut-off value of CFVR of 2.0 was used. RESULTS: The mean CFVR was 1.9 ± 0.6 in ischemic regions by CTP, whereas it was 2.9 ± 0.8 in non-ischemic regions (p < 0.001). CTP imaging could accurately predict CFVR <2.0 with 84.0% diagnostic accuracy (94.7% sensitivity, 77.4% specificity, 72.0% positive predictive value, and 96.0% negative predictive value). When receiver operating characteristic curve analysis of the MBF data was performed to detect CFVR <2.0, the area under the curve was 0.89, and the optimal MBF cut-off value was 1.43 mL/g/min. CONCLUSIONS: This study suggests that qualitative and quantitative assessment of ATP-stress CTP exhibits a good correlation with CFVR for evaluation of myocardial ischemia.