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Mathew S Maurer

Publications and source records attributed to Mathew S Maurer.

At least 19 recordsLinked to original sources
PubMed2026

Subgroups and Special Populations in Heart Failure Clinical Trials: Insights From the HFC-ARC Expert Consensus Panel.

In the evolving landscape of heart failure (HF) management, the identification and analysis of subgroups and special populations within clinical trials are crucial for enhancing clinical decision-making, guiding further research, and understanding heterogeneity in study outcomes. This expert consensus document results from the collaborative efforts of the Heart Failure Collaboratory and the Heart Failure Collaboratory Academic Research Consortium, which brought together stakeholders from academia, industry, the U.S. Food and Drug Administration, and patient representatives. The purpose of this assembly was to propose standardized definitions and critical endpoint considerations essential for shaping the design and conduct of clinical trials for drugs and devices in the field of HF. In this context, we propose definitions and endpoints for specific subgroups and special populations in the spectrum of HF. We enhanced the precision, efficacy, and applicability of clinical research and promote more "personalized" approaches to interpretation of clinical trials. Furthermore, we explore the burgeoning field of gene therapy as a promising avenue for addressing the genetic basis of certain cardiomyopathies within these specialized patient groups. We focus especially on methodological considerations for subgroup analyses in large-scale trials, highlighting the importance of proper interpretation of subgroups and best practices for identifying heterogeneity suggestive of differential treatment effects, including when these analyses should be considered hypothesis-generating and requiring subsequent validation. We advocate for a methodical approach to clinical trial design, one that prioritizes the strategic identification of subgroups and employs appropriate statistical methodologies to ensure the reliability and clinical relevance of findings. Through this lens, we envision a pathway toward more personalized and effective treatments for HF, ultimately aiming to improve patient outcomes by leveraging the insights garnered from meticulously designed and comprehensively analyzed clinical trials.

Humans↗
PubMed2026

Efficacy of Acoramidis in Wild-Type and Variant Transthyretin Amyloid Cardiomyopathy: Results From ATTRibute-CM and Its Open-Label Extension.

IMPORTANCE: Transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive disease caused by misfolded transthyretin (TTR), occurs as wild-type (ATTRwt-CM) or variant (ATTRv-CM) forms. p.Val142Ile is the most common variant in the US, linked to rapid progression and increased mortality. Acoramidis achieves near-complete (≥90%) TTR stabilization and showed clinical benefit in the 30-month ATTRibute-CM trial and through month 42 in the ongoing open-label extension (OLE). OBJECTIVE: To evaluate the efficacy of acoramidis in ATTRwt-CM, ATTRv-CM, and variant subgroups (p.Val142Ile and non-p.Val142Ile). DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, phase 3, randomized placebo-controlled study took place from April 2019 to May 2023 with ongoing OLE (month 42). ATTRibute-CM enrolled 632 participants with ATTR-CM; 611 of 632 were included in the modified intention-to-treat (mITT) population. There were 380 participants who continued into the OLE. These data were analyzed from January 2025 to July 2025. INTERVENTIONS: Oral acoramidis, 712 mg, or placebo twice daily for 30 months, followed by 12 months of open-label treatment. MAIN OUTCOMES AND MEASURES: All-cause mortality (ACM), cardiovascular-related hospitalizations (CVH), serum TTR, 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire Overall Summary score, and N-terminal pro B-type natriuretic peptide in participants with ATTRwt-CM and ATTRv-CM. Post-hoc analyses were conducted in variant subgroups, including p.Val142Ile. RESULTS: Overall, 552 participants with wild-type ATTR-CM (mean [SD] age, 78 [6.3] years; 92.0% male and 8.0% female) and 59 participants with variant ATTR-CM (mean [SD] age, 73 [7.7] years; 77.3% male and 22.7% female) were randomized (mITT population), including 35 with p.Val142Ile. Consistent efficacy was observed in wild-type and variant subgroups for ACM/CVH through month 30 and ACM through month 42. At month 30, acoramidis reduced the risk of ACM/first CVH vs placebo by 31% in ATTRwt-CM (hazard ratio [HR], 0.69; 95% CI, 0.52-0.90; P = .007) and by 59% in ATTRv-CM (HR, 0.41; 95% CI, 0.21-0.81; P = .01). ACM was reduced through month 42 with HRs of 0.70 (95% CI, 0.50-0.98; P = .04) and 0.41 (95% CI, 0.19-0.93; P = .03) in the ATTRwt-CM and ATTRv-CM groups, respectively. Consistent treatment benefit was observed in participants with ATTRwt-CM and ATTRv-CM for secondary end points. Within variant subgroups (p.Val142Ile vs non-p.Val142Ile), consistent treatment benefits were observed for ACM/CVH through month 30 and ACM through month 42. CONCLUSIONS AND RELEVANCE: The beneficial effect of acoramidis was observed consistently in ATTRwt-CM and ATTRv-CM groups. These hypothesis-generating results indicate that further studies are warranted to better characterize the therapeutic benefit of acoramidis in variant subgroups. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03860935; NCT04988386.

Humans↗
PubMed2026

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.

BACKGROUND AND AIMS: In the NEURO-TTRansform clinical trial (NCT04136184), eplontersen improved neuropathy impairment and quality of life (QoL) through Week 66 versus the NEURO-TTR historical placebo in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This analysis assessed the impact of baseline ATTRv-PN severity on eplontersen response in patients from NEURO-TTRansform. METHODS: This post hoc analysis grouped patients into tertiles by baseline Neuropathy Impairment Score (NIS): T1 (least baseline impairment: 3.5 to <&#x2009;27.5; n&#x2009;=&#x2009;67), T2 (27.5 to <&#x2009;55.0; n&#x2009;=&#x2009;67), and T3 (55.0 to <&#x2009;127.8; n&#x2009;=&#x2009;66). Outcomes assessed were neuropathy impairment (modified NIS+7 [mNIS+7] and NIS, Neuropathy Symptom and Change, Polyneuropathy Disability), QoL (Norfolk QoL-Diabetic Neuropathy), physical functioning (36-Item Short-Form Health Survey Physical Component Summary), nutritional status (modified body mass index), and serum transthyretin levels; these were compared with NEURO-TTR historical placebo. Autonomic dysfunction (Composite Autonomic Symptom Score-31), disability (Rasch-built Overall Disability Scale), and walking speed (10-Meter Walk Test) were also assessed. Final assessments were carried out following 65/66 or 81/85&#x2009;weeks of treatment. RESULTS: Mean mNIS+7 composite scores were maintained over 85&#x2009;weeks with eplontersen (changes from baseline of -4.5 [T1], -1.3 [T2], and -2.6 [T3] points). Other disease parameter scores were similarly maintained or improved with eplontersen. Patients receiving placebo experienced disease worsening across outcomes. T1 mean disease scores were typically better than in T2 and T3. INTERPRETATION: Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum.

Humans↗
PubMed2006

Single-beat estimation of end-diastolic pressure-volume relationship: a novel method with potential for noninvasive application.

Whereas end-systolic and end-diastolic pressure-volume relations (ESPVR, EDPVR) characterize left ventricular (LV) pump properties, clinical utility of these relations has been hampered by the need for invasive measurements over a range of pressure and volumes. We propose a single-beat approach to estimate the whole EDPVR from one measured volume-pressure (Vm and Pm) point. Ex vivo EDPVRs were measured from 80 human hearts of different etiologies (normal, congestive heart failure, left ventricular assist device support). Independent of etiology, when EDPVRs were normalized (EDPVRn) by appropriate scaling of LV volumes, EDPVRns were nearly identical and were optimally described by the relation EDP = An.EDV (Bn), with An = 28.2 mmHg and Bn = 2.79. V0 (the volume at the pressure of approximately 0 mmHg) was predicted by using the relation V0 = Vm.(0.6 - 0.006.Pm) and V30 by V30 = V0 + (Vm,n - V0)/(Pm/An) (1/Bn). The entire EDPVR of an individual heart was then predicted by forcing the curve through Vm, Pm, and the predicted V0 and V30. This technique was applied prospectively to the ex vivo human EDPVRs not used in determining optimal An and Bn values and to 36 in vivo human, 12 acute and 14 chronic canine, and 80 in vivo and ex vivo rat studies. The root-mean-square error (RMSE) in pressure between measured and predicted EDPVRs over the range of 0-40 mmHg was < 3 mmHg of measured EDPVR in all settings, indicating a good predictive value of this approach. Volume-normalized EDPVRs have a common shape, despite different etiology and species. This allows the entire curve to be predicted by a new method with a potential for noninvasive application. The results are most accurate when applied to groups of hearts rather than to individual hearts.

Algorithms↗
PubMed2006

The Columbia Cooperative Aging Program: an interdisciplinary and interdepartmental approach to geriatric education for medical interns.

Although there is a critical need to prepare physicians to care for the growing population of older adults, many academic medical centers lack the geriatric-trained faculty and dedicated resources needed to support comprehensive residency training programs in geriatrics. Because of this challenge at Columbia University, the Columbia Cooperative Aging Program was developed to foster geriatric training for medical interns. For approximately 60 interns each year completing their month-long geriatric rotations, an integral part of this training now involves conducting comprehensive assessments with "well" older people, supervised by an interdisciplinary team of preceptors from various disciplines, including cardiology, internal medicine, occupational therapy, geriatric nursing, psychiatry, education, public health, social work, and medical anthropology. Interns explore individual behaviors and social supports that promote health in older people; older people's strengths, vulnerabilities, and risk for functional decline; and strategies for maintaining quality of life and independence. In addition, a structured "narrative medicine" writing assignment is used to promote the interns' reflections on the assessment process, the data gathered, and their clinical reasoning throughout. Preliminary measures of the program's effect have shown significant improvements in attitudes toward, and knowledge of, older adults as patients, as well as in interns' self-assessed clinical skills. For academic medical centers, where certified geriatric providers are scarce, this approach may be an effective model for fostering residency geriatric education among interns.

Aging↗
PubMed2005

Arterial stiffness in mild primary hyperparathyroidism.

When primary hyperparathyroidism was a more symptomatic disease, it was often associated with increased cardiovascular risk. As the clinical manifestations of the disease have changed to a milder, more asymptomatic disorder, investigation is shifting to more subtle cardiovascular abnormalities. We measured arterial stiffness in 39 patients with mild primary hyperparathyroidism [serum calcium, 2.66 +/- 0.2 mmol/liter (10.7 +/- 0.6 mg/dl); PTH, 21.7 +/- 9.5 pmol/liter (89 +/- 39 pg/ml)] and in 134 controls. Arterial stiffness was measured mathematically at the radial artery with a noninvasive device as the "augmentation index" (AIx). The AIx measures the difference between the second and first systolic peaks in the pressure waveform and correlates with increased cardiovascular risk. When physiological variables affecting augmentation index and potentially confounding cardiovascular risk factors (age, gender, heart rate, height, blood pressure, diabetes mellitus, smoking, and hyperlipidemia) were adjusted for, primary hyperparathyroidism was an independent predictor of increased augmentation index (B = 3.37; P < 0.03). A matched-pair analysis showed that 15% of the variance in AIx was uniquely accounted for by the presence of primary hyperparathyroidism. The presence of primary hyperparathyroidism was a stronger predictor of elevated AIx than age, gender, smoking, hypertension, hyperlipidemia, or diabetes mellitus. AIx was also directly correlated with evidence of more active parathyroid disease, including higher PTH levels (r = +0.42; P < 0.05) and lower bone mineral density at the distal one-third radius (r = -0.33; P < 0.05). The diagnosis of primary hyperparathyroidism was therefore an independent predictor of increased AIx, an early measure of arterial stiffness, and the increase was associated with evidence of more active parathyroid disease.

Aged↗
PubMed2005

Ventriculovascular coupling in systolic and diastolic heart failure.

Pressure-volume analysis has provided critical insight into ventricular mechanics, and it has elucidated the underlying mechanisms of heart failure (HF). Renewed interest in ventriculovascular coupling, the interaction of the left ventricle and the arterial system, has developed from recent investigations focusing on the importance of heart rate control in systolic HF, blood pressure lability in the elderly, and acute pulmonary edema in patients with HF and a normal ejection fraction. These data suggest that abnormal ventriculovascular coupling may be an additional pathophysiological mechanism underlying the development of HF with a normal ejection fraction and may provide a target for novel therapies.

Animals↗
PubMed2005

Left heart failure with a normal ejection fraction: identification of different pathophysiologic mechanisms.

BACKGROUND: Although heart failure with a normal ejection fraction (HFNEF) is a clinically heterogeneous syndrome, a single pathophysiologic mechanism, diastolic dysfunction, is often ascribed to explain this condition. In view of the clinical heterogeneity of these patients, we hypothesized that subgroups of HFNEF patients may have different underlying pathophysiologic mechanisms. METHODS AND RESULTS: Freehand 3-dimensional echocardiography was used to measure left ventricular end-systolic and end-diastolic volumes in 99 asymptomatic normal controls and 2 groups with chronic heart failure: 35 patients with normal ejection fraction with longstanding hypertension (hypertensive HFNEF) and 11 patients with hypertrophic cardiomyopathy without a history of hypertension (nonhypertensive HFNEF). These data, combined with cuff sphygmomanometry and Doppler estimates of LV end-diastolic pressure (EDP) yielded estimated pressure-volume loops and slope (E es,sb ) of the end-systolic pressure-volume relationship, a load independent index of chamber contractility. Nonhypertensive HFNEF patients required high EDPs (21 +/- 2 versus 15 +/- 3 mm Hg in normals, P < .0001) to achieve normal EDVs (98 +/- 25 versus 95 +/- 21 mL in normals, P = NS). Although systolic function (E es,sb ) did not differ from normal, systolic blood pressure was lower than normal in these patients (114 +/- 10 versus 124 +/- 14 mm Hg in normals, P < .05). Hypertensive HFNEF patients also had increased EDP (20 +/- 2 mm Hg), but this was observed at higher than normal EDVs (118 +/- 29 mL, P < .05). Among patients with hypertensive HFNEF, 2 subgroups emerged, 1 with a high E es,sb (4.23 +/- 0.54 versus 2.1 +/- 0.7 mm Hg/mL) and 1 with normal E es,sb (2.31 +/- 0.51 mm Hg/mL). The former group was composed of elderly women with small body size (body surface area 1.7 +/- 0.2 versus 1.9 +/- 0.2 m 2 , P = .02) who had concentrically remodeled ventricles and low stroke volumes. The latter group was more diverse in age, body size, and included patients of both genders with increases in ventricular volumes, stroke volume, and mass consistent with a volume overload state. CONCLUSION: Although HFNEF is commonly thought of as being the result of a single hemodynamic mechanism, these data indicate that subgroups exist with distinctly different underlying pathophysiologies.

Age Factors↗
PubMed2005

Ventricular volume and length in hypertensive diastolic heart failure.

BACKGROUND: Patients with diastolic heart failure are thought to have a normal or small ventricle with impaired ventricular filling that requires increased filling pressure to maintain normal stroke volume. In this study we test the hypothesis that patients with hypertensive diastolic heart failure have increased left ventricular volumes compared with age-, sex-, and body size-matched control subjects. METHOD: Left ventricular chordal dimensions from 2-dimensional echocardiography and volumes from 3-dimensional echocardiography were obtained in control subjects (n = 96) and patients with hypertensive diastolic heart failure (n = 28) and compared before and after controlling for age, sex, and body size. RESULTS: Volumes by 3-dimensional echocardiography were significantly larger in the heart failure group than in the control group (P < .05). After matching for age, sex, and body size, volumes remained significantly larger in the patients with heart failure (P < .05). Chordal dimensions were not significantly different between the two groups. Stroke volume and centerline length of the ventricle were significantly increased in the heart failure group compared with matched control subjects (P < .05). CONCLUSIONS: Our group of patients with hypertensive diastolic heart failure had significantly increased left ventricular volumes and stroke volume compared with control subjects, compatible with volume overload heart failure. Two-dimensional echocardiographic measurement of the ventricular chordal dimension failed to detect this enlargement. Ventricular length appeared to be preferentially increased in the patients with hypertensive diastolic heart failure.

Aged↗
PubMed2005

Diabetes mellitus is associated with an increased risk of falls in elderly residents of a long-term care facility.

BACKGROUND: Diabetes mellitus is common among elderly persons, with several potential complications that could contribute to falls. However, diabetes mellitus is not widely recognized as an important risk factor for falls among elderly persons. Accordingly, the purpose of the current study was to determine whether diabetes is an independent risk factor for falls in elderly residents of a long-term care facility. METHODS: Ours was a prospective cohort study of 139 elderly (88 +/- 7 years, range 70-105 years), Caucasian (97%) residents (women, 84%) of a long-term care facility. Inclusion criteria were age > or = 60 years, ability to rise from a seated position, informed consent obtained from participant or guardian. Multiple domains were assessed for the association with falls including: clinical diagnoses; medication use; orthostatic changes in blood pressure, gait, or balance; cognitive/mental status; general well being; activities of daily living; affect/behavior; range of motion and/or ambulation; and communication. Diabetes mellitus was determined by use of hypoglycemic agents. Time to first fall was determined by review of daily New York State mandated "Incident and Accident" reports. RESULTS: Over the follow-up period (mean 299 days), 49 participants (35%) experienced a fall. The fall incidence rate for the participants with and without diabetes mellitus was 78% and 30%, respectively (p <.001). The significant unadjusted hazard ratios of fall risk factors included diabetes mellitus, Berg Balance Scale score <45, number of medications, angiotensin-converting enzyme (ACE) inhibitors, hypertension, use of assistive device, inability to independently move a wheelchair, and use of antidepressants, with the latter two factors being protective. In multivariate analysis, only diabetes (adjusted hazard ratio 4.03; 95% confidence interval, 1.96-8.28) and gait and balance (adjusted hazard ratio 5.26; 95% confidence interval, 1.26-22.02) were significantly and independently associated with an increased risk of falls. CONCLUSIONS: Our results suggest that diabetes mellitus is an independent fall risk factor among elderly nursing home residents.

Accidental Falls↗
PubMed2004

Role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure.

Although present in many patients with heart failure and a normal ejection fraction, the role of isolated impairments in active myocardial relaxation in the genesis of elevated filling pressures is not well characterized. Because of difficulties in determining the effect of prolonged myocardial relaxation in vivo, we used a cardiovascular simulated computer model. The effect of myocardial relaxation, as assessed by tau (exponential time constant of relaxation), on pulmonary vein pressure (PVP) and left ventricular end-diastolic pressure (LVEDP) was investigated over a wide range of tau values (20-100 ms) and heart rate (60-140 beats/min) while keeping end-diastolic volume constant. Cardiac output was recorded over a wide range of tau and heart rate while keeping PVP constant. The effect of systolic intervals was investigated by changing time to end systole at the same heart rate. At a heart rate of 60 beats/min, increases in tau from a baseline to extreme value of 100 ms cause only a minor increase in PVP of 3 mmHg. In contrast, at 120 beats/min, the same increase in tau increases PVP by 23 mmHg. An increase in filling pressures at high heart rates was attributable to incomplete relaxation. The PVP-LVEDP gradient was not constant and increased with increasing tau and heart rate. Prolonged systolic intervals augmented the effects of tau on PVP. Impaired myocardial relaxation is an important determinant of PVP and cardiac output only during rapid heart rate and especially when combined with prolonged systolic intervals. These findings clarify the role of myocardial relaxation in the pathogenesis of elevated filling pressures characteristic of heart failure.

Blood Pressure↗
PubMed2004

Diastolic dysfunction: can it be diagnosed by Doppler echocardiography?

Heart failure with a normal ejection fraction (HFNEF) predominantly afflicts older, female individuals and is considered to be a consequence of diastolic dysfunction. Doppler echocardiography has become the standard method for identifying and characterizing diastolic function. However, the important distinction between Doppler measures of filling dynamics and true indexes of intrinsic ventricular diastolic chamber properties is not widely appreciated. Herein, we delineate physiologic measures of intrinsic ventricular diastolic function, as determined by pressure volume analysis, and compare and contrast these measures with those derived from Doppler echocardiography. Doppler-derived indexes of ventricular filling do not provide specific information on intrinsic passive diastolic properties, and thus, abnormal filling dynamics do not necessarily equate with intrinsic myocardial diastolic dysfunction. This raises a fundamental question as to whether delayed relaxation and/or stiffened passive properties are the unifying pathophysiologic mechanisms in all patients who present with HFNEF.

Aged↗
PubMed2002

Myocardial contraction fraction: a volumetric index of myocardial shortening by freehand three-dimensional echocardiography.

OBJECTIVES: This study sought to evaluate myocardial contraction fraction (MCF) as an index of myocardial shortening by comparison to conventional shortening indices in patients with hypertensive hypertrophy, athletes with physiologic hypertrophy and sedentary normal adult subjects. BACKGROUND: A significant percentage of patients with hypertensive hypertrophy have "normal" or "preserved" left ventricular (LV) systolic function by conventional echocardiographic measures whereas their systolic function is depressed when measured by the two-dimensional echocardiographic mid-wall shortening fraction (MWSF). A three-dimensional echocardiographic measure of myocardial shortening analogous to MWSF has been lacking. We describe a volumetric measure of myocardial shortening, the MCF, as the ratio of stroke volume (SV) to myocardial volume (MV), and hypothesize that it may be useful to compare myocardial performance in patients with different degrees and types of hypertrophy. METHODS: We compared the MCF using freehand three-dimensional echocardiographic reconstruction of the LV to conventional measures of LV function (ejection fraction [EF], endocardial shortening fraction [SF] and MWSF) in subjects with pathologic hypertensive hypertrophy, heart failure symptoms and preserved EF (n = 17), athletes with physiologic hypertrophy (n = 41) and normal sedentary adults (n = 80). RESULTS: The EF was in the normal range for all three groups. The MCF was lower in hypertensive hypertrophy compared with normal subjects (0.33 +/- 0.05 vs. 0.44 +/- 0.07, p < 0.01). It also successfully differentiated physiologic hypertrophy from normal subjects (0.50 +/- 0.05 vs. 0.44 +/- 0.07, p < 0.01). The endocardial SF did not distinguish athletes from normal subjects and the MWSF did not distinguish hypertensive from physiologic hypertrophy. CONCLUSIONS: The MCF, a volumetric measure of myocardial shortening, demonstrates that myocardial shortening is decreased in hypertensive hypertrophy and increased in physiologic hypertrophy. The MCF may be useful in assessing differences in myocardial performance in patients with similar degrees of hypertrophy.

Adult↗