Sigmoidal heart rate response pattern during exercise in patients with chronic heart failure.

Detailed heart rate (HR) response patterns during exercise in patients with heart failure (HF) and sinus rhythm remain uncertain. We screened consecutive patients with HF who underwent cardiopulmonary exercise tests at a large academic center from November 2013 to July 2023. HR response during exercise was statistically classified using logistic differential equation models. A total of 99 patients were included. Of them, 75 patients were assigned to "sigmoidal pattern" and the other 24 to "exponential pattern." Patients with the sigmoidal pattern were older and exhibited higher plasma B-type natriuretic peptide levels. Increases in HR and oxygen consumption (V̇o2)/kg up to the anaerobic threshold level were not different between both patterns. However, beyond the threshold, the sigmoidal pattern group showed no further increase in HR and significantly lower V̇o2/kg than their counterparts (interactions for P < 0.001). HR response during exercise in patients with heart failure and sinus rhythm was categorized into two unique groups: sigmoidal and exponential patterns. More detailed clarification of the sigmoidal pattern, potentially indicating sinus node dysfunction, should offer new clinical insights for chronotropic incompetence.NEW & NOTEWORTHY Heart rate response patterns can be classified into two groups among patients with chronic heart failure reaching maximal exertion: sigmoidal and exponential.

Successful management of HeartMate 3 in a patient with arrhythmogenic right ventricular cardiomyopathy.

The management of right heart failure during durable left ventricular assist device (LVAD) support remains an unsolved issue so far. We had a 44-year-old male patient who was diagnosed with arrhythmogenic right ventricular cardiomyopathy and received HeartMate 3 LVAD (Abbott, USA) implantation as a bridge-to-transplant indication. The pump speed was adjusted as low as 4500 rpm to avoid the left ventricular narrowing and interventricular septal leftward shift. Riociguat was administered to decrease the afterload of the right ventricle and increase the preload of the left ventricle, in addition to the combination of neurohormonal blockers. Frequent low-flow alarm events eventually disappeared after amlodipine administration, and he was successfully returned to work. We here present a unique management in a patient with right heart failure due to arrhythmogenic right ventricular cardiomyopathy during HeartMate 3 LVAD support.

A case of destination therapy for post-fulminant myocarditis with myelodysplastic syndrome.

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome.

Effect of Optimal Heart Rate on Left Ventricular Remodeling in Patients with Systolic Heart Failure Following Acute Coronary Syndrome.

The optimal therapeutic approach to facilitate reverse remodeling is desired in patients with systolic heart failure following acute coronary syndrome (ACS). The association between heart rate (HR) and reverse remodeling in this cohort has remained elusive.Patients with left ventricular ejection fraction (LVEF) < 50% who received echocardiography assessments following ACS were retrospectively included. Theoretically ideal HR was calculated using a previously established formula: 93 - 0.13 × (deceleration time [msec]). Impacts of HR on echocardiographic left ventricular (LV) reverse remodeling during the 2-year observational period were compared between 2 groups stratified by the HR difference between theoretically ideal and actual values: optimal HR group (HR difference ≤ 10 bpm) versus sub-optimal HR group (HR difference > 10 bpm).A total of 27 patients (median 72 years old, 23 males) were included. There were no significant differences in the baseline characteristics including maximum serum creatinine kinase level and the dose of beta-blocker between the 2 groups. LV ejection fraction increased significantly only in the optimal HR group at follow-up (from 42% to 54%; P = 0.001). The optimal HR group exhibited a more pronounced decrease in LV end-diastolic diameter (from 57 to 52 mm) compared to the sub-optimal HR group (from 58 to 56 mm).Optimal HR, which was calculated using a previously proposed formula, was associated with more substantial post-infarct LV reverse remodeling. The implications of aggressive HR modulation targeting theoretically ideal HR among those with systolic heart failure following ACS are the focus of our investigation here.

Efficacy of Doppler echocardiography-guided ivabradine therapy.

BACKGROUND: The purpose of this study was to evaluate the advantage of heart rate (HR) modulation using ivabradine referring Doppler echocardiography over the conventional ivabradine therapy without echocardiography guide in patients with systolic heart failure. METHODS: From October 2020, our institute updated the protocol of ivabradine therapy, in which HR was optimized to minimize the overlap between the two left ventricular inflow waves using Doppler echocardiography (echo-guided group). The degree of cardiac reverse remodeling at 3-month follow-up was compared between the echo-guided group and the conventional ivabradine therapy group treated before October 2020. RESULTS: A total of 28 patients (62 years old, 17 men) were included, and 18 patients were from echo-guided group. Left ventricular ejection fraction increased significantly in the echo-guided group (from 41% [28%, 49%] to 55% [37%, 66%], p = 0.007), whereas it remained unchanged in the conventional group (p = 0.333). Systolic blood pressure and the daily dose of carvedilol increased significantly only in the echo-guided group (p = 0.009 and p = 0.001, respectively). CONCLUSIONS: Among those with systolic heart failure, a Doppler echocardiography guide might be a promising therapeutic tool in modulating HR by ivabradine in facilitating reverse remodeling.

Remote dielectric sensing and lung ultrasound to assess pulmonary congestion.

We investigated the agreement between remote dielectric sensing (ReDS) system, which is a recently introduced non-invasive technology to quantify the degree of pulmonary congestion, and lung ultrasound (LUS), which is a gold standard to assess the existence of severe pulmonary congestion. Consecutive patients who were hospitalized to examine the cause of heart failure and treat their heart failure in our institute were prospectively included. They received LUS and simultaneous ReDS measurements. Three or more B-lines at each LUS zone was assigned to B-profile positive, indicating the existence of significant pulmonary congestion. ReDS values ≥ 35% were defined as significant pulmonary congestion. A total of 19 heart failure patients were included (77 years, 13 men). Plasma B-type natriuretic peptide level was 131 (36, 416) pg/ml. Three patients had B-profile, indicating significant pulmonary congestion, and two of them had ≥ 35% of ReDS (sensitivity 66.7%, specificity 87.5%, and negative predictive value 93.3%). Most of the patients (79%) had lower B-lines below 3 and did not satisfy the criteria of B-profile, irrespective of wide ranges of ReDS values. ReDS system had as acceptable predictability as LUS in assessing the existence of significant pulmonary congestion. ReDS would be recommended to rule out significant pulmonary congestion or quantify the degree of less significant pulmonary congestion.

Changes in lung fluid levels with variations in the respiratory cycle.

The association between respirophasic variation and lung fluid levels is unknown. Remote dielectric sensing (ReDS™) is a novel non-invasive technology to quantify lung fluid levels. We investigated the change in ReDS values over the course of the respiratory cycle. Patients with clinically stable chronic heart failure at outpatient clinics were prospectively included. ReDS values were measured at three respiratory statuses and compared: (1) at rest with normal breathing, (2) at inspiration, and (3) at expiration. A total of 11 patients were included. Median age was 73 (58, 78) years and 9 were men. ReDS value was 28% (25%, 32%) at rest and decreased significantly with inspiration down to 26% (24%, 30%) (p = 0.004). ReDS value were significantly higher on expiration as 30% (27%, 34%) as compared with rest (p = 0.003). Lung fluid levels in chronic heart failure patients can vary with changes in the respiratory cycle-attention should be paid to what point in the respiratory cycle measurements are taken when interpreting results in each modality, such as chest X-ray (measured at inspiratory status) and right heart catheterization (measured at expiratory status). ReDS system might be a physiologically ideal modality to assess lung fluid amount under natural breathing.

Prognostic impact of remote dielectric sensing value following TAVR.

Remote dielectric sensing (ReDS) system non-invasively quantifies pulmonary congestion. Re-admission following trans-catheter aortic valve replacement (TAVR) remains an unsolved matter. Residual pulmonary congestion is a strong risk factor of worse clinical outcomes in patients with heart failure. ReDS system may have a prognostic impact in patients undergoing TAVR. Patients who received TAVR and ReDS measurements during index hospitalization between 2021 and 2022 were included. The prognostic impact of ReDS value on the composite endpoint of death or re-admission following index discharge was investigated. Totally, 42 patients (median 84 years, 14 men) were included. Median ReDS value at index discharge was 27% (24%, 30%) and 10 patients had ReDS values > 30%. During a median of 316 (282, 354) days following index discharge, a higher ReDS value at baseline was independently associated with the incidence of composite endpoint with an adjusted hazard ratio of 1.32 (95% confidence interval between 1.10 and 1.58) with a calculated cutoff of 30%, which significantly stratified the cumulative incidence of the composite endpoint (78% in the high ReDS group [N = 10] and 36% in the normal ReDS group [N = 32], p = 0.002). ReDS technology may be a promising tool to predict future clinical outcomes following TAVR by quantifying residual pulmonary congestion. The clinical implication of ReDS-guided aggressive intervention following TAVR remains the next concern.

Feasibility and Efficacy of Exercise Training Concomitant with Re-Assessment of Medical Therapy in Patients with Heart Failure Receiving Intravenous Inotropes.

Exercise training in addition to re-assessment of medical treatments is recommended for patients with advanced heart failure. However, the feasibility and efficacy of exercise training in patients with heart failure receiving intravenous inotropes remains uncertain.Clinical data were analyzed from consecutive patients with stabilized hemodynamics receiving intravenous inotropes for more than 1 week and undergoing cardiac rehabilitation at our institute between February 2020 and May 2022. All patients received re-assessment of guideline-directed medical therapy and non-pharmacological treatment, in addition to the exercise therapy. The intensity of exercise training was determined based on the results of cardiopulmonary exercise testing.A total of 10 patients receiving intravenous inotropes (median age 60 years, left ventricular ejection fraction 23%) were included. All patients received low-dose dobutamine and 4 patients received concomitant milrinone. Exercise training was continued for 112 days on median without any critical complications. Intravenous inotropes were continued for 41 days on median and weaned off in all patients. Plasma B-type natriuretic peptide decreased slightly from 291 (129, 526) to 177 (54, 278) pg/mL (P = 0.070) and peak oxygen consumption increased from 10.0 (8.3, 15.3) to 15.2 (10.9, 17.2) mL/kg/minute (P = 0.142) during the 6-month observational period following the initiation of exercise intervention.Exercise training might be feasible and effective in patients with advanced heart failure receiving low-dose intravenous inotrope support concomitant with re-assessment of medical treatment.

Association Between Remote Dielectric Sensing and Body Mass Index.

Remote dielectric sensing (ReDS) is a non-invasive, electromagnetic energy-based technology to quantify pulmonary congestion. However, the accuracy of ReDS values in patients with a variety of physiques has not been fully validated.Prospective successive measurements of ReDS values and body mass index (BMI) were performed on admission in consecutive hospitalized patients with cardiovascular diseases. Patients were stratified into 4 groups according to the WHO classification: underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 24.9), pre-obese (25.0 ≤ BMI < 29.9), and obese (30.0 ≤ BMI). The indexed ReDS value was defined as a ReDS value divided by the modified congestion score index (the severity of pulmonary congestion on chest X-ray). The indexed ReDS values were compared among the 4 stratified groups.A total of 436 patients (76 [69, 82] years old and 254 men) were included. The median indexed ReDS values were 21.3 (19.1, 23.8), 25.7 (21.0, 29.5), 25.7 (20.3, 31.0), and 28.0 (21.1, 34.0) in underweight, normal weight, pre-obese, and obese patients, respectively, highlighting the underweight group had the lowest values (P < 0.001).ReDS values may be underestimated and specific caution should be paid in its interpretation in underweight patients.

Combination Treatment of Balloon Pulmonary Angioplasty and Direct Oral Anticoagulant in a Patient with Chronic Thromboembolic Pulmonary Hypertension Complicated by Protein S Deficiency.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a phenotype of pulmonary hypertension due to chronic and multiple organized thrombus. The therapeutic strategy for patients with CTEPH and comorbid protein S deficiency remains unknown due to its rarity. Case: We encountered a 49-year-old male patient with CTEPH and concomitant mild protein S deficiency (type III). We could successfully perform balloon pulmonary angioplasty without any major complications, including thromboembolism and bleeding, followed by standard-dose oral anticoagulation therapy instead of warfarin. Conclusion: A currently established standard therapeutic strategy for CTEPH, including pulmonary angioplasty, may be safe and effective even in patients with concomitant inherent coagulation abnormalities.

Therapeutic Strategy for Patients with Concomitant Pulmonary Artery Hypertension and Hypertrophic Obstructive Cardiomyopathy: A Rare Case Report.

Combined cases of hypertrophic obstructive cardiomyopathy (HOCM) and pulmonary arterial hypertension (PAH) are rare and have a management dilemma. Although preload is crucial in the management of HOCM, anti-PAH agents dramatically change the preload, leading to improving or worsening heart failure in patients with HOCM. We had a 74-year-old woman with Sjogren-syndrome-associated PAH. Her heart failure worsened following the initiation of anti-PAH agents due to an incremental preload on the left ventricle, whereas HOCM clinically developed following the termination of anti-PAH agents and progressing anorexia due to the progression of the left ventricular outflow obstruction. Careful monitoring of the left ventricular outflow obstruction during initiation/termination of anti-PAH agents and medical intervention to the HOCM are highly recommended.

The Association Between Sleeping Pill Use and Metabolic Syndrome in an Apparently Healthy Population in Japan: JMS-II Cohort Study.

BACKGROUND: Sleeping pills are widely used for sleep disorders and insomnia. This population-based study aimed to evaluate the association between the use of sleeping pills and metabolic syndrome (MetS) and metabolic components in an apparently healthy Japanese cohort. METHODS: We examined baseline cross-sectional data from the JMS-II Cohort Study. The criteria for MetS and its components were based on The National Cholesterol Education Program Adult Treatment Panel III. Sleep habits including the sleep duration of the subjects and the frequency of sleeping pill use were obtained using The Pittsburgh Sleep Quality Index questionnaire. For different sleep durations, the association between sleeping pill use and MetS was assessed. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using multiple logistic regression models to quantify this association. RESULTS: Our study included 6,153 individuals (mean age, 63.8 [standard deviation 11.2] years), and 3,348 (54.4%) among them were women. The association between sleep duration and MetS was an inverted J-shaped curve among sleeping pill users and a J-shaped curve among non-users. After adjustment for various confounders, less than 6 h of sleep among sleeping pill users was associated with increased rates of MetS (<6 h, OR 3.08; 95% CI, 1.29-7.34]). The frequency of sleeping pill use in individuals with short sleep duration showed a positive association with the prevalence of MetS and its components. CONCLUSIONS: Sleeping pill users with a short sleep duration had a 3-fold higher chance of having MetS than non-users with a short sleep duration.

The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus.

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin's osmotic diuresis mechanism, patients' serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (ß1=-0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e' tended to decrease (ß1=-0.382, p=0.13, LRA). Compared to the baseline, E/e' was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e' group (E/e'≥10, n=34), E/e' decreased significantly (ß1=-0.63, p<0.05, LRA). ΔE/e' was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e' in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function.

Therapeutic Strategy for Heart Failure with Reduced Ejection Fraction and Cardiac Amyloidosis.

We sometimes encounter patients with systolic heart failure and cardiac amyloidosis. Neurohormonal blockers are guideline-directed medical therapy for those with systolic heart failure. However, its implication among the above cohort remains controversial. Of 3 patients with systolic heart failure and cardiac amyloidosis who we encountered, cardiac reverse remodeling was achieved in 2 patients who received neurohormonal blockers, whereas cardiac function remained unchanged in a patient not receiving neurohormonal blockers. Neurohormonal blockers might be keys to achieve cardiac reverse remodeling and favorable clinical outcomes even in patients with systolic heart failure and cardiac amyloidosis, although further larger-scale studies are required to validate our hypothesis.

Correlation Between Plasma B-Type Natriuretic Peptide Levels and Remote Dielectric Sensing in Patients with Heart Failure.

Plasma B-type natriuretic peptide (BNP) is a practical tool with which to estimate hemodynamic status including intra-cardiac pressure in patients with heart failure (HF). However, plasma BNP levels cannot be measured immediately in an outpatient private clinic. We investigated the value of remote dielectric sensing (ReDS), a novel non-invasive electromagnetic energy-based tool to quantify lung fluid amount immediately, to predict plasma BNP levels.Successive measurements of ReDS values and plasma BNP levels were performed in patients hospitalized to treat HF in a prospective manner. Correlations between ReDS values and plasma BNP levels were assessed.A total of 117 datasets for HF patients were obtained in this prospective study. The median ReDS value was 28% (interquartile range: 25%, 34%) and the median plasma BNP level was 205 (86, 469) pg/mL, both of which had a slight correlation (r = 0.234, P = 0.011). Their correlation improved when those with a body mass index less than 18.5 (n = 23) were excluded (r = 0.278, P = 0.007).ReDS might be a practical tool for estimating plasma BNP levels, particularly in outpatient private clinics where the immediate measurement of plasma BNP levels is not available.

Impact of optimal heart rate on left ventricular reverse remodeling and functional improvement in patients with systolic heart failure.

Heart rate modulation therapy using ivabradine reduces mortality and morbidity in patients with systolic heart failure, whereas too reduced heart rate seems to worsen the clinical outcome. The optimal heart rate during heart rate modulation therapy remains unknown. Consecutive patients with left ventricular ejection fraction < 50% who received echocardiographic assessments and simultaneous heart rate measurements were retrospectively investigated. Theoretically ideal heart rate was calculated using a previously proposed formula: 93 - 0.13 × (deceleration time [msec]). Impacts of heart rate on the 1-year echocardiographic left ventricular reverse remodeling were compared among the three groups stratified by the heart rate status: optimal heart rate group (within 10 bpm of ideal heart rate), below-optimal heart rate group (< 10 bpm of ideal heart rate), and above-optimal heart rate group (> 10 bpm of ideal heart rate). A total of 75 patients (70 years old, 60 men) were included. There were no significant differences in the baseline characteristics among the three groups, except for the higher prevalence of tolvaptan use and higher plasma B-type natriuretic peptide level in the below-optimal heart rate group. Left ventricular end-diastolic diameter (from 55 to 54) and left ventricular ejection fraction (from 39 to 46) improved significantly only in the optimal heart rate group at 1-year follow-up (p < 0.05 for both). Optimal heart rate, which was calculated using a formula consisting of deceleration time, was associated with cardiac reverse remodeling in patients with systolic heart failure. Prospective study to investigate the implication of deceleration time-guided aggressive heart rate optimization is the next concern.

How to Estimate the Optimal Heart Rate in Patients with Heart Failure with Preserved Ejection Fraction.

Ideal heart rate (HR), particularly for those with heart failure with preserved ejection fraction (HFpEF), remains unknown. We hypothesized that cardiac output would be maximum when the overlap between E-wave and A-wave at the trans-mitral flow is "zero" in the Doppler echocardiography. We retrospectively investigated the association among the overlap length between two waves, actual HR, and other echocardiographic parameters to construct a formula for estimating theoretically ideal HR among those with HFpEF. In total, 48 HFpEF patients were included (70-year-olds, 18 males). Given the results of multivariate linear regression analyses, the overlap length was estimated as follows: -1,050 + 8.4 × (HR [bpm]) + 0.6 × (deceleration time [millisecond]) + 1.7 × (A-width [millisecond]), which had a strong agreement with the actually measured overlap length (r = 0.86, P < 0.001). Theoretically ideal HR was calculated by substituting zero into the estimated overlap length as follows: 125 - 0.07 × (deceleration time [millisecond]) - 0.20 × (A-width [millisecond]). In the validation cohort including another 143 HFpEF patients, the estimated overlap using the formula again had a strong agreement with the actually measured overlap (r = 0.72, P < 0.001). In this study, we proposed a novel formula for calculating theoretically ideal HR, consisting of deceleration time and A-width, in the HFpEF cohort. Clinical implication to optimize the HR targeting the theoretically ideal HR should be investigated in prospective studies.

Acute Heart Failure in a Patient with Occult Barlow's Disease Receiving Bevacizumab.

Bevacizumab is a recombinant humanized monoclonal antibody and a key drug for treatment of various types of cancer. Bevacizumab is associated with the occurrence of heart failure, but its risk factors remain unknown. A 55-year-old woman was diagnosed with cervical cancer, which was completely treated by bevacizumab-incorporated chemotherapy. During the 9-month bevacizumab therapy, she suffered from hypertension requiring multiple antihypertensive agents. She was admitted to our hospital due to acute heart failure with afterload mismatch and severe mitral regurgitation. A transesophageal echocardiography showed Barlow's disease with a degenerated and widely prolapsed mitral valve. She received a scheduled surgical mitral valve repair. Post-operative cause was uneventful, but metastatic dissemination developed later. The existence of mitral valve regurgitation, even when sub-clinical, might be a risk of worsening heart failure during bevacizumab therapy. Careful follow-up at an onco-cardiology clinic is highly encouraged particularly for such a cohort during bevacizumab therapy.