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Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention (PROSe-ICD)
Katherine Wu, MD - kwu@jhmi.edu
NCT00733590
Inclusion Criteria:
* History of acute MI at least 4 weeks old
* Non-ischemic LV dysfunction for at least 9 months
* Who have an ejection fraction (EF) \< or = to 35%
* Undergone elective replacement indicator (ERI) generator replacement of an FDA-approved ICD for primary prevention of SCD within 24 months of enrollment.
* Who have primary prevention implants.
Exclusion Criteria:
* ICD generator replacement for secondary prevention
* Inability or unwillingness to provide valid informed consent
* New York Heart Association Class IV heart failure
* Patients with pre-existing Class 1 indications for pacemaker therapy. Heart Failure, Congestive, Death, Sudden, Cardiac, Arrhythmia, Cardiomyopathies
defibrillator, implanted, genomics, electrocardiography, electrophysiological study, proteomics
Diuretics Alone vs. Aortix Endovascular Device for Acute Heart Failure (DRAIN-HF)
Rubi Reyes-Fuentez - rubi@procyrion.com
NCT05677100
Inclusion Criteria (Randomized Study):
* Currently admitted to the hospital with a primary diagnosis of decompensated heart failure, irrespective of ejection fraction (EF);
* Patients should be on maximally tolerated diuretic therapy and not diuresing sufficiently before being enrolled in DRAIN-HF. After being up-titrated on diuretics, patients should be followed for at least 24 hours on the higher of: i) furosemide 80 mg IV bid or equivalent or ii) IV furosemide or equivalent IV loop diuretic at a dose 2.5 x total daily home dose of furosemide equivalents in 2 divided doses, as tolerated, patient must have: Urine Output \<1,500mL in a 12-hour period OR a Net Fluid Loss ≤375mL in a 12-hour period.
* Persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema, elevated jugular venous pressure \>12 cm water or ascites after treatment with IV diuretics per inclusion criterion 2.;
* Age \>21 years and able to provide written informed consent;
* Negative pregnancy test if patient is of child-bearing potential.
Exclusion Criteria (Randomized Study):
* Treatment with high dose IV inotropes within the last 48 hours prior to enrollment. High dose is defined as \>5 µg/kg/min dopamine OR \>5 µg/kg/min dobutamine OR \>0.375 µg/kg/min milrinone;
* Active and ongoing hypotension with a systolic blood pressure \<90 mmHg lasting more than 30 minutes or a mean arterial pressure (MAP) \<60 mmHg lasting more than 30 minutes at enrollment;
* Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours prior to enrollment;
* An estimated PASP of \>80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure;
* Acute kidney failure defined as an increase in serum creatinine to ≥4.0mg/dL (≥353.6 µmol/L) at enrollment;
* Evidence of contrast induced nephropathy, nephritis or nephrotic syndrome;
* Prior kidney transplant, single kidney, partial nephrectomy OR use of dialysis, continuous renal replacement therapy (CRRT) or ultrafiltration in the last 90 days prior to enrollment;
* Confirmed decompensated cirrhosis (defined as Child Pugh class B or C) or concern for shock liver (AST \> 1000U/L or total Bilirubin \> 5.0mg/dl) at enrollment;
* Presence of an active, uncontrolled infection that would preclude safe placement or removal of the device;
* Prior heart transplant or likely heart transplantation before the 30- day follow-up visit;
* Current or previous support with a durable LVAD at any time or planned LVAD insertion before the 30-day follow-up visit;
* Use of an intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), or percutaneous ventricular assist devices (e.g. Impella or TandemHeart) within the last 30 days;
* Confirmed diagnosis of AL amyloidosis;
* Acute myocardial infarction Type 1 within 30 days of enrollment, or planned coronary revascularization in the next 30 days;
* Stroke within 30 days of enrollment;
* Severe Bleeding Risk (any of the following):
• Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days,
• GI bleeding within 6 months requiring hospitalization and/or transfusion,
• Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding,
• Procedure with arterial ilio-femoral access \> 6 FR within 30 days,
• Platelet count \<75,000 cells/mm3,
• Uncorrectable bleeding diathesis or coagulopathy (e.g. INR ≥2 not due to anticoagulation therapy) or hypercoaguable state including HIT;
• Inability to tolerate anticoagulation therapy for up to 7 days. * Contraindicated Anatomy :
• Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\],
• Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21F (outer diameter) introducer sheath,
• Femoral artery depth inconsistent with use of closure device,
• Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g. aneurysm with thrombus, marked tortuosity, significant narrowing or inadequate size of the abdominal aorta, iliac or femoral arteries, or severe calcification),
• Known connective tissue disorder (e.g. Marfan Syndrome) or other aortopathy at risk of vascular injury,
• Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging. * Known hypersensitivity or contraindication to study or procedure medications (e.g. anticoagulation therapy) or device materials (e.g. history of severe reaction to nickel or nitinol); * Participation in any other clinical investigation that is likely to confound study results or affect the study; * Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit; * Unable or unwilling to undergo screening (imaging, PA Catheter placement), device implant and retrieval procedures or return for 30-day visit. Inclusion Criteria (Advanced Heart Failure Registry): * Currently admitted to the hospital with a primary diagnosis of decompensated HF, irrespective of ejection fraction (EF). * Patient has already been evaluated and indicated to receive an LVAD or heart transplant and will receive the LVAD or be listed for heart transplantation in the next 30 days if their congestion status and renal function improves. * Patient must have been treated with ≥ 80 mg IV furosemide bid or equivalent and have evidence of increasing diuretic dosing requirements over the past 12 months, as tolerated. * Must have evidence of refractoriness to medical management as documented by persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema, elevated jugular venous pressure \>12 cm water, or ascites after treatment with IV diuretics for a minimum of 24 hours. * Serum creatinine ≥ 2.0 mg/dL AND eGFR ≤ 45 ml/min/1.73m2 at time of enrollment * Age ≥ 21 years and able to provide written informed consent. * Negative pregnancy test if patient is of childbearing potential. Exclusion Criteria (Advanced Heart Failure Registry): * Treatment with high dose IV inotropes within 48 hours prior to enrollment. High dose is defined as any one of the following: \>5 µg/kg/min dopamine OR \>5 µg/kg/min dobutamine OR \>0.375 µg/kg/min milrinone. * Active and ongoing hypotension with a systolic blood pressure \<80 mmHg lasting more than 30 minutes or a mean arterial pressure (MAP) \<55 mmHg lasting more than 30 minutes at enrollment. * Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours prior to enrollment. * An estimated PASP of \>80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure. * Acute kidney failure defined as an increase in serum creatinine to ≥ 4.0mg/dL at enrollment. * Evidence of contrast-induced nephropathy, nephritis, or nephrotic syndrome. * Prior kidney transplant, single kidney, partial nephrectomy OR use of dialysis, continuous renal replacement therapy (CRRT), or ultrafiltration in the last 90 days prior to enrollment. * Confirmed decompensated cirrhosis (defined as Child Pugh class B or C) or concern for shock liver (AST \> 1000U/L or total Bilirubin \> 5.0mg/dl) at enrollment. * Presence of an active, uncontrolled infection that would preclude safe placement or removal of the device. * Current or previous support with a durable LVAD. * INTERMACS Profile 1 at enrollment. * Currently on mechanical ventilatory support. * Use of an intra-aortic balloon pump (IABP) within the last 14 days or use of an extracorporeal membrane oxygenation (ECMO) or percutaneous ventricular assist device (e.g., Impella or TandemHeart) within the last 30 days. * Confirmed diagnosis of AL amyloidosis. * Acute myocardial infarction Type 1 within 30 days of enrollment or planned coronary revascularization in the next 30 days. * Stroke within 30 days of enrollment. * Severe Bleeding Risk (any of the following): * Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days. * GI bleeding within 6 months requiring hospitalization and/or transfusion. * Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding. * Procedure with arterial ilio-femoral access \> 6 Fr within 30 days. * Platelet count \<75,000 cells/mm3 . * Uncorrectable bleeding diathesis or coagulopathy (e.g., INR≥ 2 not due to anticoagulation therapy) or hypercoagulable state including HIT. * Inability to tolerate anticoagulation therapy for up to 7 days. * Contraindicated Anatomy : * Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\]. * Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21 Fr (outer diameter) introducer sheath. * Femoral artery depth inconsistent with use of closure device. * Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g., aneurysm with thrombus; marked tortuosity; significant narrowing or inadequate size of the abdominal aorta, iliac, or femoral arteries; or severe calcification). * Known connective tissue disorder (e.g., Marfan Syndrome) or other aortopathy at risk of vascular injury. * Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging. * Known hypersensitivity or contraindication to study or procedure medications (e.g., anticoagulation therapy) or device materials (e.g., history of severe reaction to nickel or nitinol). * Participation in any other clinical investigation that is likely to confound study results or affect the study. * Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit. * Unable or unwilling to undergo screening, device implant and retrieval procedures, or return for 30-day visit.
• Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days,
• GI bleeding within 6 months requiring hospitalization and/or transfusion,
• Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding,
• Procedure with arterial ilio-femoral access \> 6 FR within 30 days,
• Platelet count \<75,000 cells/mm3,
• Uncorrectable bleeding diathesis or coagulopathy (e.g. INR ≥2 not due to anticoagulation therapy) or hypercoaguable state including HIT;
• Inability to tolerate anticoagulation therapy for up to 7 days. * Contraindicated Anatomy :
• Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\],
• Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21F (outer diameter) introducer sheath,
• Femoral artery depth inconsistent with use of closure device,
• Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g. aneurysm with thrombus, marked tortuosity, significant narrowing or inadequate size of the abdominal aorta, iliac or femoral arteries, or severe calcification),
• Known connective tissue disorder (e.g. Marfan Syndrome) or other aortopathy at risk of vascular injury,
• Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging. * Known hypersensitivity or contraindication to study or procedure medications (e.g. anticoagulation therapy) or device materials (e.g. history of severe reaction to nickel or nitinol); * Participation in any other clinical investigation that is likely to confound study results or affect the study; * Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit; * Unable or unwilling to undergo screening (imaging, PA Catheter placement), device implant and retrieval procedures or return for 30-day visit. Inclusion Criteria (Advanced Heart Failure Registry): * Currently admitted to the hospital with a primary diagnosis of decompensated HF, irrespective of ejection fraction (EF). * Patient has already been evaluated and indicated to receive an LVAD or heart transplant and will receive the LVAD or be listed for heart transplantation in the next 30 days if their congestion status and renal function improves. * Patient must have been treated with ≥ 80 mg IV furosemide bid or equivalent and have evidence of increasing diuretic dosing requirements over the past 12 months, as tolerated. * Must have evidence of refractoriness to medical management as documented by persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema, elevated jugular venous pressure \>12 cm water, or ascites after treatment with IV diuretics for a minimum of 24 hours. * Serum creatinine ≥ 2.0 mg/dL AND eGFR ≤ 45 ml/min/1.73m2 at time of enrollment * Age ≥ 21 years and able to provide written informed consent. * Negative pregnancy test if patient is of childbearing potential. Exclusion Criteria (Advanced Heart Failure Registry): * Treatment with high dose IV inotropes within 48 hours prior to enrollment. High dose is defined as any one of the following: \>5 µg/kg/min dopamine OR \>5 µg/kg/min dobutamine OR \>0.375 µg/kg/min milrinone. * Active and ongoing hypotension with a systolic blood pressure \<80 mmHg lasting more than 30 minutes or a mean arterial pressure (MAP) \<55 mmHg lasting more than 30 minutes at enrollment. * Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours prior to enrollment. * An estimated PASP of \>80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure. * Acute kidney failure defined as an increase in serum creatinine to ≥ 4.0mg/dL at enrollment. * Evidence of contrast-induced nephropathy, nephritis, or nephrotic syndrome. * Prior kidney transplant, single kidney, partial nephrectomy OR use of dialysis, continuous renal replacement therapy (CRRT), or ultrafiltration in the last 90 days prior to enrollment. * Confirmed decompensated cirrhosis (defined as Child Pugh class B or C) or concern for shock liver (AST \> 1000U/L or total Bilirubin \> 5.0mg/dl) at enrollment. * Presence of an active, uncontrolled infection that would preclude safe placement or removal of the device. * Current or previous support with a durable LVAD. * INTERMACS Profile 1 at enrollment. * Currently on mechanical ventilatory support. * Use of an intra-aortic balloon pump (IABP) within the last 14 days or use of an extracorporeal membrane oxygenation (ECMO) or percutaneous ventricular assist device (e.g., Impella or TandemHeart) within the last 30 days. * Confirmed diagnosis of AL amyloidosis. * Acute myocardial infarction Type 1 within 30 days of enrollment or planned coronary revascularization in the next 30 days. * Stroke within 30 days of enrollment. * Severe Bleeding Risk (any of the following): * Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days. * GI bleeding within 6 months requiring hospitalization and/or transfusion. * Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding. * Procedure with arterial ilio-femoral access \> 6 Fr within 30 days. * Platelet count \<75,000 cells/mm3 . * Uncorrectable bleeding diathesis or coagulopathy (e.g., INR≥ 2 not due to anticoagulation therapy) or hypercoagulable state including HIT. * Inability to tolerate anticoagulation therapy for up to 7 days. * Contraindicated Anatomy : * Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\]. * Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21 Fr (outer diameter) introducer sheath. * Femoral artery depth inconsistent with use of closure device. * Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g., aneurysm with thrombus; marked tortuosity; significant narrowing or inadequate size of the abdominal aorta, iliac, or femoral arteries; or severe calcification). * Known connective tissue disorder (e.g., Marfan Syndrome) or other aortopathy at risk of vascular injury. * Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging. * Known hypersensitivity or contraindication to study or procedure medications (e.g., anticoagulation therapy) or device materials (e.g., history of severe reaction to nickel or nitinol). * Participation in any other clinical investigation that is likely to confound study results or affect the study. * Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit. * Unable or unwilling to undergo screening, device implant and retrieval procedures, or return for 30-day visit.
DEVICE: Aortix System
Heart Failure, Cardiorenal Syndrome, Cardio-Renal Syndrome, ADHF, Heart Failure, Systolic, Heart Failure, Diastolic, Heart Failure, With Decompensation, Heart Failure, Congestive
mechanical circulatory support, percutaneous
Treating Heart Dysfunction Related to Cancer Therapy With Sacubitril/Valsartan (TREAT-HF)
Massey CTO CPC Team - masseycpc@vcu.edu
Bottinor, Wendy
NCT05194111
HM20023601
Inclusion Criteria:
* Age \/=40% on echocardiogram or cardiac MRI
* No symptoms of heart failure (shortness of breath, fatigue, swelling). Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).
Exclusion Criteria:
* -Age \<18 years
* Inability to obtain consent from patient or legally authorized representative
* Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent compliance with study instructions
* Limited English or Spanish proficiency that in the opinion of the investigator may prevent understanding the content of the informed consent form or safely completing the study procedures
* Participation in another concurrent intervention study within 30 days or treatment with an investigational drug within 5 half-lives prior to randomization
* Greater than mild mitral or aortic valve regurgitation/stenosis known pre-cancer therapy
* Severe kidney disease (GFR \<30 mL/min/1.73m2)
* Chronic hyperkalemia (\>5mmol/L)
* Evidence of COVID-19 within the last 60 days or recent (21 days) exposure to close personal contact with COVID-19.
* Greater than moderate tricuspid or pulmonary valve regurgitation/stenosis known pre-cancer therapy
* Hemodynamically significant congenital heart disease in the opinion of the investigator (not including PFO/small ASD or small VSD)
* Greater than moderate pericardial effusion
* Constrictive cardiomyopathy diagnosed pre-cancer therapy
* Family history of genetic cardiomyopathy
* Evidence of infiltrative cardiomyopathy
* Symptomatic heart disease based on NYHA classification
* Allergy to valsartan or sacubitril
* Inability to complete CMR or 6-minute walk test
* Inability to measure non-invasive blood pressure and heart rate in the ambulatory/home setting
* Pregnant/lactating
* History of severe hypersensitivity reactions to gadolinium-based contrast agents (will perform limited cardiac imaging without contrast)
* Concomitant use of other ACE inhibitors or ARBs, aliskiren, NSAIDs or lithium or the inability to stop these medications for the study DRUG: Sacubitril-valsartan, DRUG: Valsartan
Heart Failure, Heart Dysfunction
Left vs Left Randomized Clinical Trial
Mihail G Chelu, MD, PhD - leftvsleft@bcm.edu
NCT05650658
Inclusion Criteria:
* Men and women 18 years of age or older.
* A LVEF ≤ 50% within 6 months prior to enrollment.
* Resting QRS duration ≥130 ms as evidenced by a historical 12-lead ECG prior to enrollment OR anticipated right ventricular pacing \>40% OR device in place with right ventricular pacing \> 40%.
* Are optimized on HF guideline directed medical therapy according to current HF published guidelines OR patient's physician will make an effort to start all guideline-directed medical therapy and titrate doses up as permitted by the participant clinical status and co-morbidities prior to implantation procedure.
Exclusion Criteria:
* Women who are pregnant, lactating, or plan to become pregnant during the course of the trial.
* Participants with angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary, intervention in the next three (3) months.
* Enzyme-positive myocardial infarction within the past three (3) months prior to enrollment.
* Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past three (3) months prior to enrollment.
* Reversible non-ischemic cardiomyopathy (e.g., acute viral myocarditis).
* Participants with Chagas disease, cardiac sarcoidosis or amyloidosis.
* Expected to receive left ventricular assist device or heart transplantation within 6 months.
* Participants with primary severe valvular disease (e.g., aortic stenosis).
* Have a life expectancy of less than 12 months.
* Participants with irreversible brain damage from preexisting cerebral disease.
* Participants with a contrast dye allergy unable or unwilling to undergo pretreatment with steroids and/or diphenhydramine.
* Participants participating in any other interventional cardiovascular clinical trial.
* Participants who would be unable to comply with the study's follow-up visit schedule; or
* Participants who had any prior unsuccessful attempt at implantation of biventricular pacing (BiVP), His Bundle Pacing (HBP), or Left Bundle Branch Pacing (LBBP) device. DEVICE: His/LBBP, DEVICE: BiVP
Heart Failure, Heart Failure With Reduced Ejection Fraction, AV Block, LBBB, RBBB, Intraventricular Conduction Delay, Pacing-Induced Cardiomyopathy
Cardiac Resynchronization Therapy in Previously Untreatable and High Risk Upgrade Patients (SOLVE-CRT)
Nicholas Vesom - clinical@ebrsystemsinc.com
Ellenbogen, Kenneth, A
NCT02922036
HM20014794
Inclusion/Exclusion:
Inclusion Criteria
• Patient with a class I or IIa (1) or (2) indication for implantation of a CRT-D device according to current available guidelines (with additional QRS criteria on Class IIa (1)):
• Class I: NYHA II, III, IV, EF ≤ 35%, LBBB, QRS ≥ 150ms
• Class IIa (1): NYHA II, III, IV, EF≤ 35%, LBBB, QRS ≥ 130 to < 150ms
• Class IIa (2): NYHA II, III, IV, EF≤ 35%, non-LBBB, QRS ≥ 150ms
• Patient is a:
• 'Non-responder' [Not Enrolling]: Patients who have a CRT system that is functional and despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and attempts at optimal device programming the patient has not responded to therapy for a minimum of 6 months. Non-response is defined as:
• EF has remained unchanged or worsened (defined as < 5% increase since implant), and
• The patient's clinical status based in the totality of available clinical evidence (such as NYHA Class, exercise tolerance, QOL, or global assessment) has remained unchanged or worsened, as determined by the local Site Enrollment Committee OR
• 'Previously Untreatable': Patients who have a full or partial CRT system, who meet general inclusion criteria and are deemed as 'previously untreatable' for one of the following reasons: i. Patients in whom CS lead implantation for CRT has failed
• CS lead implant was attempted but abandoned due any of the following: difficult CS access or anatomy, inadequate lead location, inadequate pacing thresholds, persistent phrenic nerve pacing, or other procedural challenges ii. CS lead implanted but has been programmed OFF
• LV lead that was implanted but not operational includes patients in whom the LV lead is inoperative or programmed off due to improper function such as high threshold, non-capture, phrenic nerve pacing, lead failure, lead dislodgement, or sub-optimal LV lead location OR c. 'High Risk Upgrade: Patients who have a relative contraindication to CS lead implant, due to:
• venous occlusion or lesion precluding implant
• pocket infection risk (at co-implanted device site)
• considered high risk for CS implant due to co-morbidities
• Patients on a stable Guideline Directed Medical Therapy (GDMT)
• Patient must be 18 years old or over
• Patient has signed and dated informed consent
• Patient has suitable anatomy for implant of the WiSE CRT System (e.g. adequate acoustic window, LV wall thickness in target implant area ≥ 5 mm, absence of LV wall structural abnormalities which may preclude implant) Exclusion Criteria Patients who meet any one of these criteria will be excluded from the investigation:
• Pure RBBB
• LVEDD ≥ 8cm
• Non-ambulatory or unstable NYHA class IV
• Contraindication to heparin, chronic anticoagulants or antiplatelet agents
• Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy
• Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days.
• Patients with planned or expected lithotripsy treatment post implant
• Life expectancy of < 12 months
• Chronic hemodialysis
• Stage 4 or 5 renal dysfunction defined as eGFR < 30
• Grade 4 mitral valve regurgitation
• Noncardiac implanted electrical stimulation therapy devices
• Patients with a prosthetic aortic valve in which the electrode cannot be implanted via a transseptal approach
• Patients with a prosthetic mitral valve in which the electrode cannot be implanted via a retrograde aortic approach
• Unstable angina, acute MI, CABG, or PTCA within the past 1 month
• Correctable valvular disease that is the primary cause of heart failure
• Recent CVA or TIA (within the previous 3 months)
• Patients with a history of paroxysmal or persistent atrial fibrillation/flutter are excluded if they have had a documented AF episode > 30 min or a cardioversion in the past 1 month.
• Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing <95%)
• Already included in another clinical study that could confound the results of this study
• Pregnancy
• Known drug or alcohol addiction or abuse
• Moderate or severe aortic stenosis
• Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, or to comply with the trial's procedures
• For Part II Randomized patients only, those who will not tolerate being randomized to the Control Group for 6 months
• Patient with a class I or IIa (1) or (2) indication for implantation of a CRT-D device according to current available guidelines (with additional QRS criteria on Class IIa (1)):
• Class I: NYHA II, III, IV, EF ≤ 35%, LBBB, QRS ≥ 150ms
• Class IIa (1): NYHA II, III, IV, EF≤ 35%, LBBB, QRS ≥ 130 to < 150ms
• Class IIa (2): NYHA II, III, IV, EF≤ 35%, non-LBBB, QRS ≥ 150ms
• Patient is a:
• 'Non-responder' [Not Enrolling]: Patients who have a CRT system that is functional and despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and attempts at optimal device programming the patient has not responded to therapy for a minimum of 6 months. Non-response is defined as:
• EF has remained unchanged or worsened (defined as < 5% increase since implant), and
• The patient's clinical status based in the totality of available clinical evidence (such as NYHA Class, exercise tolerance, QOL, or global assessment) has remained unchanged or worsened, as determined by the local Site Enrollment Committee OR
• 'Previously Untreatable': Patients who have a full or partial CRT system, who meet general inclusion criteria and are deemed as 'previously untreatable' for one of the following reasons: i. Patients in whom CS lead implantation for CRT has failed
• CS lead implant was attempted but abandoned due any of the following: difficult CS access or anatomy, inadequate lead location, inadequate pacing thresholds, persistent phrenic nerve pacing, or other procedural challenges ii. CS lead implanted but has been programmed OFF
• LV lead that was implanted but not operational includes patients in whom the LV lead is inoperative or programmed off due to improper function such as high threshold, non-capture, phrenic nerve pacing, lead failure, lead dislodgement, or sub-optimal LV lead location OR c. 'High Risk Upgrade: Patients who have a relative contraindication to CS lead implant, due to:
• venous occlusion or lesion precluding implant
• pocket infection risk (at co-implanted device site)
• considered high risk for CS implant due to co-morbidities
• Patients on a stable Guideline Directed Medical Therapy (GDMT)
• Patient must be 18 years old or over
• Patient has signed and dated informed consent
• Patient has suitable anatomy for implant of the WiSE CRT System (e.g. adequate acoustic window, LV wall thickness in target implant area ≥ 5 mm, absence of LV wall structural abnormalities which may preclude implant) Exclusion Criteria Patients who meet any one of these criteria will be excluded from the investigation:
• Pure RBBB
• LVEDD ≥ 8cm
• Non-ambulatory or unstable NYHA class IV
• Contraindication to heparin, chronic anticoagulants or antiplatelet agents
• Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy
• Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days.
• Patients with planned or expected lithotripsy treatment post implant
• Life expectancy of < 12 months
• Chronic hemodialysis
• Stage 4 or 5 renal dysfunction defined as eGFR < 30
• Grade 4 mitral valve regurgitation
• Noncardiac implanted electrical stimulation therapy devices
• Patients with a prosthetic aortic valve in which the electrode cannot be implanted via a transseptal approach
• Patients with a prosthetic mitral valve in which the electrode cannot be implanted via a retrograde aortic approach
• Unstable angina, acute MI, CABG, or PTCA within the past 1 month
• Correctable valvular disease that is the primary cause of heart failure
• Recent CVA or TIA (within the previous 3 months)
• Patients with a history of paroxysmal or persistent atrial fibrillation/flutter are excluded if they have had a documented AF episode > 30 min or a cardioversion in the past 1 month.
• Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing <95%)
• Already included in another clinical study that could confound the results of this study
• Pregnancy
• Known drug or alcohol addiction or abuse
• Moderate or severe aortic stenosis
• Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, or to comply with the trial's procedures
• For Part II Randomized patients only, those who will not tolerate being randomized to the Control Group for 6 months
Device: WiSE System
Heart Failure
A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Heart Failure and Inflammation (HERMES)
Novo Nordisk - clinicaltrials@novonordisk.com
NCT05636176
Inclusion Criteria:
* Serum high-sensitivity C-reactive protein (hs-CRP) greater than equal to 2 milligrams per liter (mg/L) at screening (visit 1) Disease specific - cardiovascular
* At least one of the following:
• N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than equal to 300 picograms per milliliter (pg/mL) at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NTproBNP must be greater than equal to 600 pg/mL. Note that the screening electrocardiogram (ECG) must be obtained the same day as sampling for NT-proBNP.
• Hospitalisation or urgent/unplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the last 9 months prior to screening (visit 1) in combination with NT-proBNP greater than equal to 200 pg/mL at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NT-proBNP must be greater than equal to 600 pg/mL. * Diagnosis of heart failure (New York Heart Association \[classification\] \[NYHA\] Class II-IV). * Left ventricular ejection fraction (LVEF) greater than 40 percentage (%) documented by echocardiography within 12 months prior to or at screening (visit 1). The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (e.g., myocardial infarction \[MI\] or heart failure \[HF\] hospitalisation). * Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening (visit 1) showing at least one of the following: * Left atrial (LA) volume index greater than 34 milliliter per meter square (mL/m\^2). * LA diameter greater than equal to 3.8 centimeter (cm). * LA length greater than equal to 5.0 cm. * LA area greater than equal to 20 cm square. * LA volume greater than equal to 55 milliters (mL). * Intraventricular septal thickness greater than equal to 1.1 cm. * Posterior wall thickness greater than equal to 1.1 cm. * Left ventricular (LV) mass index greater than equal to 115 grams per meter square (g⁄m\^2 ) in men or greater than equal to 95 g⁄m\^2 in women. * E/e' (mean septal and lateral) greater than equal to 10. * e' (mean septal and lateral) less than 9 centimeter per second (cm/s). * No heart failure hospitalisations or urgent heart failure visits between screening (visit 1) and randomisation (visit 2).
Exclusion Criteria:
Medical conditions - cardiovascular
* Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation, within 30 days prior to screening (visit 1).
* Systolic blood pressure greater than equal to 180 millimeters of mercury (mmHg) at screening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patient should be receiving greater than equal to 3 antihypertensive drugs. (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
* Heart rate above 110 or below 40 beats per minute as evaluated on the electrocardiogram (ECG) performed at screening (visit 1) (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
* Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1). (Note: Planned coronary angiogram is not exclusionary).
* Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period (visit 1).
* Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2).
* Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primary valve disease.
* Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
* Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism).
Medical conditions - infections/immunosuppression
\- Clinical evidence of, or suspicion of, active infection at the discretion of the investigator. DRUG: Ziltivekimab, DRUG: Placebo
Heart Failure
The Effects of IL-1 Blockade on Inotrope Sensitivity in Patients With Heart Failure (AID-HEART) (AID-HEART)
Benjamin VanTassell - bvantassell@vcu.edu
NCT06062966
Inclusion Criteria:
* Primary diagnosis for the clinic visit is stage D heart failure being on chronic stable dose of inotrope therapy (dobutamine or milrinone for the previous 28 days)
* Prior documentation of impaired left ventricular systolic function (ejection fraction \<50%) at most recent assessment by any imaging modality (within 12 months)
* Stable dose of inotrope treatment without a recent hospitalization within the previous month
* Age ≥21 years and willing/able to provide written informed consent
* The patient is willing and able to comply with the protocol (i.e. self administration of the treatment, and exercise protocol).
* Screening plasma C-reactive protein levels \>2 mg/L
Exclusion Criteria:
* Concomitant clinically significant comorbidities including (but not limited to) acute coronary syndromes, uncontrolled hypertension or orthostatic hypotension, tachy- or brady-arrhythmias, acute or chronic pulmonary disease or neuromuscular disorders affecting respiration that would interfere with the execution, interpretation, or completion of the study
* Recent (previous 3 months) or planned resynchronization therapy (CRT), or valve surgeries
* Previous or planned implantation of left ventricular assist devices or heart transplant within the next 3 months
* Recent (\<14 days) use of immunosuppressive or anti-inflammatory drugs (including oral corticosteroids at a dose of prednisone equivalent of 0.5 mg/kg/day but not including inhaled or low dose oral corticosteroids or non-steroidal anti-inflammatory drugs)
* Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus)
* Active infection (of any type), including chronic/recurrent infectious disease (including HBV, HCV, and HIV/AIDS) - but excluding HCV+ with undetectable plasma RNA
* Prior (within the past 5 years) or current malignancy on targeted treatment - excluding carcinoma in situ \[any location\] or localized non-melanoma skin cancer
* Stage V kidney disease or on renal-replacement therapy
* Neutropenia (\<1,500/mm3 or \<1,000/mm3 in African-American patients)
* Pregnancy or breastfeeding
* Angina, hypertension, arrhythmias, electrocardiograph (ECG) changes, or other non-cardiac limitations that limit 6MWD obtained during the baseline testing
* Hypersensitivity to anakinra or to E. coli derived products DRUG: Anakinra
Heart Failure
Inotrope sensitivity, IL-1 Blockade, Subcutaneous (SC), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV, 6 Minute Walk Test (6MWT)
Impact of Bromocriptine on Clinical Outcomes for Peripartum Cardiomyopathy (REBIRTH)
Dennis McNamara, MD - mcnamaradm@upmc.edu
NCT05180773
Inclusion Criteria:
• Presentation with a new diagnosis of peripartum cardiomyopathy
• Post-delivery and within the first 5 months post-partum.
• Clinical assessment of an LVEF \< or =0.40 within 4 weeks of consent for randomized control trial
• Clinical assessment of an LVEF \< or =0.40 within 8 weeks of consent for breastfeeding cohort
• Age \> or = 18.
Exclusion Criteria:
• Previous diagnosis of cardiomyopathy, valvular disease or congenital heart disease (with the exception of women with a history of peripartum cardiomyopathy with complete recovery and a documented LVEF \> 0.55 prior to or in early pregnancy)
• Refractory hypertension (Systolic \>160 or Diastolic \> 95) either at the time of enrollment or at the time of the qualifying LVEF.
• Postpartum women currently breastfeeding and planning to continue.
• Evidence of coronary artery disease (\>50% stenosis of major epicardial vessel or positive non-invasive stress test)
• Previous cardiac transplant
• Current durable LVAD support
• Currently requiring support with extracorporeal membrane oxygenation (ECMO)
• Current history of alcohol or drug abuse
• Chemotherapy or chest radiation within 5 years of enrollment
• Evidence of ongoing bacterial septicemia
• Medical, social or psychiatric condition which limit the ability to comply with follow-up.
DRUG: Bromocriptine, DRUG: Placebo, DRUG: Guideline Directed Medical Therapy for Heart Failure (GDMT), DRUG: Rivaroxaban, DRUG: Second Placebo
Peripartum Cardiomyopathy, Postpartum
A Research Study Looking Into How Ziltivekimab Works Compared to Placebo in Participants With Heart Failure and Inflammation (ATHENA)
Novo Nordisk - clinicaltrials@novonordisk.com
NCT06200207
Inclusion Criteria:
* Serum high-sensitivity C-reactive protein (hs-CRP) greater than or equal to 2 milligrams per liter (mg/L) at screening (visit 1)
* Disease specific - cardiovascular:
* N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than or equal to 225 picograms per milliliter (pg/mL) (375 pg/mL for participants with atrial fibrillation/flutter) at screening
* Diagnosis of heart failure (New York heart association (NYHA) Class II-III)
* Left ventricular ejection fraction (LVEF) greater than 40 percent documented by echocardiography within 12 months prior to or at screening (visit 1). The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (example myocardial infarction (MI) or heart failure (HF) hospitalisation)
* Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening (visit 1) showing at least one of the following:
• Left atrial (LA) volume index greater than 34 milliliter per square meter (mL/m\^2)
• LA diameter greater than or equal to 3.8 centimeter (cm)
• LA length greater than or equal to 5.0 cm
• LA area greater than or equal to 20 square centimeter (cm\^2)
• LA volume greater than or equal to 55 milliliter (mL)
• Intraventricular septal thickness greater than or equal to 1.1 cm
• Posterior wall thickness greater than or equal to 1.1 cm
• LV mass index greater than or equal to 115 gram per square meter (g/m\^2) in men or greater than or equal to 95 g/m\^2 in women h) E/e' (mean septal and lateral) greater than or equal to 10 i) e' (mean septal and lateral) less than 9 centimeter per second (cm/s) * No heart failure hospitalisations or urgent heart failure visits between screening and randomisation * Able to perform the 6-minute walk test (6MWT) at screening with a minimum distance of 100 metres * Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score lesser than 80 at screening
Exclusion Criteria:
* Medical conditions - cardiovascular:
* Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation within 30 days prior to screening (visit 1)
* Systolic blood pressure greater than or equal to 180 millimeters of mercury (mmHg) at screening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patient should be receiving greater than or equal to 3 antihypertensive drugs
* Heart rate above 110 or below 40 beats per minute as evaluated on the Electrocardiogram (ECG) performed at screening (visit 1)
* Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1)
* Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period (visit 1)
* Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2)
* Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primary valve disease
* Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including chronic obstructive pulmonary disease (COPD)
* Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism)
* Medical conditions - infections/immunosuppression:
* Clinical evidence of, or suspicion of, active infection at the discretion of the investigator DRUG: Ziltivekimab, DRUG: Placebo
Heart Failure, Systemic Inflammation
Fluid Management of Acute Decompensated Heart Failure Subjects Treated With Reprieve System (FASTR-II) (IDE-G210258) (FASTR-II)
Annemarie Forrest - aforrest@reprievecardio.com
NCT06898515
Inclusion Criteria:
• Diagnosis of HF with expected hospitalization \>24 hours, with \>1 new or worsening symptom and \>2 physical examination, laboratory, or invasive findings of HF, and receiving or with plans to receive a HF-specific treatment
• ≥10 lb. (4.5 kg) above dry weight as estimated by health care provider.
• Current outpatient prescription for daily loop diuretic.
• Participants ≥ 22 years of age able to provide informed consent and comply with study procedures.
• Elevated risk of diuretic resistance, as indicated by at least one of the following: Baseline hypochloremia OR Urine output \<1L in the 6 hours following IV loop diuretic \>=40 mg furosemide equivalent OR Spot urine sodium \<100 mmol/L 1-2 hours after IV loop diuretic \>= 40 mg furosemide equivalent
Exclusion Criteria:
• Urologic issues that would predispose the participant to a high rate of urogenital trauma or infection with catheter placement or known inability to place a Foley catheter.
• Hemodynamic instability as defined by any of the following: sustained systolic blood pressure \<90 mmHg for \>15 minutes within the past 48 hours, use of IV vasopressors or inotropes within past 48 hours, and/or current or previous mechanical circulatory support within the last week.
• Uncontrolled arrhythmias defined as sustained HR \>130 beats/min for \>10 minutes within the past 48 hours.
• Severe lung disease with chronic home oxygen requirement \>2L/min.
• Acute infection with evidence of systemic involvement (e.g., clinically suspected infection with fever or elevated serum white blood cell count).
• Estimated glomerular filtration rate (eGFR) \<25 ml/min/1.73m2 (calculated with either MDRD or CKD-EPI) or current use of renal replacement therapy (RRT).
• Significant left ventricular outflow obstruction, severe uncorrected complex congenital heart disease, known severe stenotic valvular disease, severe infiltrative or constrictive cardiomyopathy or other diagnosis that would make aggressive decongestion unsafe.
• Current or recent (\< 30 days) type I myocardial infarction (e.g., acute coronary syndrome such as NSTEMI or STEMI from plaque rupture), coronary artery bypass surgery, or stroke. An isolated troponin elevation (e.g., from volume overload or demand ischemia) is not a reason for exclusion.
• Severe electrolyte abnormalities (e.g., serum potassium \<3.0 mEq/L, magnesium \<1.3 mEq/L or sodium \<125 mEq/L). Note: These are based on baseline/screening labs. Participants whose electrolyte levels are repleted cannot be reassessed for inclusion in the trial.
• Other concomitant disease or condition the investigator believes will make it difficult to follow instructions or comply with study procedures and/or follow-up visits, including expected prolonged hospitalization for reasons other than decongestive therapy
• Currently enrolled in an interventional trial (observational studies are permitted).
• Life expectancy less than 6 months.
• Women who are pregnant or breastfeeding.
DEVICE: Reprieve System, DRUG: furosemide infusion
Acute Decompensated Heart Failure
His-Bundle Corrective Pacing in Heart Failure (HIS-CRT)
Ann Colasurdo - ann.colasurdo@heart.rochester.edu
NCT05265520
Inclusion Criteria:
* Age 18 years or older (no upper age limit)
* Optimal medical therapy for heart failure by current guidelines
* Class IIa or IIb guideline-based indication for CRT-D implant in RBBB patients, including one of the following:
* New York Heart Association (NYHA) class II HF symptoms, LVEF ≤ 30% and QRS≥ 150 ms (IIb); OR
* NYHA class III-IV a HF, LVEF ≤ 35%, and QRS duration ≥ 150 ms (IIa); OR
* NYHA class III-IV a HF, LVEF ≤ 35%, and QRS duration 120-149 ms (IIb)
Exclusion Criteria:
* Unable to obtain most recent imaging data from echocardiogram within 1 year prior to date of randomization
* Left bundle branch block (LBBB) or intraventricular conduction delay (IVCD) ECG morphology
* Unable or unwilling to follow study protocol
* Less than 12 months life expectancy at consent
* Pregnancy or planned pregnancy during duration of the study
* On heart transplant list or likely to undergo heart transplant PROCEDURE: His-CRT implantation, PROCEDURE: BIV-CRT implantation
Right Bundle-Branch Block, Heart Failure, His-bundle Pacing, Cardiac Resynchronization Therapy
Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Gowda, Madhu, S
NCT01790152
HM20000463
Inclusion Criteria:
Study Strata I, II, and III are closed for further patient entry as of March 31, 2021. The study remains open for existing medical record submission of Stratum IV
* STRATUM I AND STRATUM II: LEUKEMIA AND LYMPHOMA SURVIVORS
* Previously enrolled leukemia and lymphoma survivors, randomized to + or - DRZ on P9404, P9425, P9426, or DFCI 95-01 (high-risk patients only)
* STRATUM I: Alive and in continuous first complete remission from their original cancer (leukemia/lymphoblastic lymphoma \[P9404, high-risk DFCI 95-01\] or Hodgkin lymphoma \[P9425/P9426\])
* STRATUM I: Did not have progressive disease or induction failure requiring off-protocol therapy including hematopoietic cell transplantation
* STRATUM I: Must not have been diagnosed with any subsequent malignancy that required additional cardiotoxic therapies (i.e., radiotherapy to the chest \[also includes fields directed towards the neck, upper abdomen, or spine\], or additional anthracyclines or anthraquinones); patients with history of subsequent malignancy that did not require such therapies remain eligible
* STRATUM I: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM II: Among leukemia and lymphoma patients randomized to + or - DRZ on P9404, P9425, P9426, and DFCI 95-01 (high risk patients only) who have relapsed or have experienced a subsequent malignancy that precludes eligibility since their original diagnosis, the study committee will review the available data (both from Children's Oncology Group's \[COG?s\] Statistics and Data Center \[SDC\] and the participating institution) to determine if individual patients are to be selected for Stratum 2; in recognition that local institutions sometimes have more updated relapse/subsequent cancer data than SDC, in cases where local data is more updated, local data will be used preferentially; the study will petition the Institutional Review Board (IRB) specifically for a waiver of consent to include any relapse and subsequent cancer data obtained from existing records for analysis of the secondary aims; patients selected for Stratum 2 will be those for whom late relapse or subsequent cancer is reported but who lack clear confirmation in existing records (either at SDC or at the local institution)
* STRATUM II: Alive, but have experienced relapse of their original cancer and/or have developed a subsequent cancer (other than non-melanomatous skin cancer) since their original diagnosis
* STRATUM II: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM III: OSTEOSARCOMA SURVIVORS
* Previously enrolled osteosarcoma survivors treated on P9754 who are alive and able (themselves and/or parents/legal guardian) to provide written informed consent; note that relapse and subsequent malignancy are not exclusion criteria for P9754 survivors
* Comparison subjects for P9754 survivors will be eligible to be enrolled from any ALTE11C2 participating COG site (even if that institution did not participate on P9754), according to the following criteria:
* Newly diagnosed, previously untreated biopsy-proven moderate or high grade osteosarcoma without metastasis; patients with low grade osteosarcoma, parosteal or periosteal sarcoma are ineligible
* \< 31 years of age at time of initial osteosarcoma diagnosis
* Diagnosis occurred between January 1, 1999 through December 31, 2002; duration of therapy can extend beyond 2002
* No evidence of poor or low cardiac function at time of initial osteosarcoma diagnosis; if reports from the time are available: shortening fraction \>= 28% by echocardiogram and within the institutional normative range for age, or radionuclide angiogram ejection fraction \>= 50%; if imaging reports from the time are no longer available, there must be no documentation within available medical records that suggest poor or low cardiac function at time of diagnosis
* Comparison subject must have institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) documenting lifetime receipt of 450 to 600 mg/m\^2 of doxorubicin (doses within 10% are acceptable); this includes initial therapy as well as any subsequent therapy for relapse or second cancer, if relevant; as such, comparison subjects who have had osteosarcoma relapse or subsequent malignancies remain eligible so long as they meet all other eligibility criteria
* No anthracycline or anthraquinone aside from doxorubicin was ever given as part of initial or subsequent therapies
* No exposure to DRZ at any point in time
* All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM IV: CARDIOMYOPATHY CASES, NOT OTHERWISE ELIGIBLE FOR STRATUMS 1, 2, AND 3
* Individuals diagnosed with cancer prior to age 21 years, who required treatment with chemotherapy and/or radiotherapy, achieved initial remission, and remained alive after completing anti-cancer-therapy for at least 1 year
* Must have screening echocardiograms for heart function as part of cancer therapy and off-therapy evaluations available (Digital Imaging and Communications in Medicine \[DICOM\] format). Images from Video Home System (VHS) tapes and reports only (without images) are not suitable
* Cannot have a known history of congenital heart disease (patent foramen ovale remain eligible) or underlying genetic syndrome associated with abnormal cardiovascular development or health (e.g., down syndrome)
* Based on echocardiography, must have either left ventricular fractional shortening =\< 28.0% or ejection fraction =\< 50.0% on at least two occasions, with at least one of these measurements occurring after cancer therapy completion and be in the absence of sepsis or any uncontrolled infection
* If the fractional shortening or ejection fraction criteria is only met on one occasion, this must be after cancer therapy completion, be in the absence of sepsis or any uncontrolled infection, and the patient must have subsequently started on chronic medical therapy for cardiomyopathy (e.g., beta-blocker, angiotensin-converting enzyme \[ACE\]-inhibitor, angiotensin receptor blocker) lasting at least 6 months
* For all participants (stratums 1, 2, 3, and 4), all institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met OTHER: Assessment of Therapy Complications, OTHER: Laboratory Biomarker Analysis, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Hodgkin Lymphoma in Remission, Leukemia in Remission, Lymphoblastic Lymphoma, Osteosarcoma, Recurrent Leukemia, Recurrent Lymphoma, Recurrent Malignant Neoplasm
Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having HFpEF (Rebalance-HF)
Judit Adorjan - j.adorjan@axontherapies.com
Shah, Keyur, B
NCT04592445
HM20022228
Inclusion Criteria
• Chronic heart failure, defined as:
• Symptoms of HF requiring current (intermittent or continuous) treatment with diuretics for \>30 days, AND
• NYHA class II with a history of \>NYHA class II in the past year, NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening or signs of HF (any rales post cough, chest x-ray demonstrating pulmonary congestion), AND
• At least one of the following: i. ≥1 HF hospital admission (with HF as the primary diagnosis) including treatment with intravenous (IV) diuretics or urgent unplanned treatment with IV diuretics in healthcare facility within past 12 months, OR ii. NT-proBNP \>300 pg/ml in normal sinus rhythm (\>450 pg/ml in atrial fibrillation or flutter) within the past 6 months; BNP \>100 pg/ml in normal sinus rhythm (\>300 pg/ml in atrial fibrillation or flutter) within the past 6 months, OR iii. Right heart catheterization (RHC) with PCWP ≥ with PCWP ≥18 mmHg at rest or 25 mmHg during exercise at the time of the screening RHC.
• Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2022 ACCF/AHA Guideline for the Management of Heart Failure (Class 1 and 2a recommendations), with no significant changes \[≥100% increase or ≥50% decrease\] for a minimum of 1 month (30 days) prior to screening, that is expected to be maintained without change for at least 6 months. Participants cannot have started a glucagon-like peptide (GLP)-1 or gastric inhibitory peptide (GIP) agonist within the last 6 months or plan to start a GLP-1 or GIP agonist within the ensuing 6 months after enrollment.
• LVEF ≥50% (site-determined by transthoracic echocardiography) within the past 6 months.
• Age ≥40 years.
• Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.
• MI (type I) and/or percutaneous cardiac intervention within 3 months prior to screening; CABG in past 3 months prior to screening, or current indication for coronary revascularization.
• Cardiac resynchronization therapy initiated within 3 months prior to screening.
• Advanced heart failure defined as one or more of the following:
• ACC/AHA/ESC Stage D HF or non-ambulatory NYHA Class IV HF.
• Inotropic infusion (continuous or intermittent) within 6 months prior to screening.
• Subject is on the cardiac transplant waiting list.
• Presence of or prior history of mechanical circulatory support for HF.
• Poor left heart compliance as determined by pulse-wave Doppler transmitral early-to-late (E/A) ratio \>2.0 assessed by the screening echocardiogram. The Screening Committee will evaluate left heart function if the transmitral A velocity is not measurable or absent.
• Right heart dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) \<12 mm or right ventricular (RV) fractional area change (FAC) \<25% assessed by the screening echocardiogram.
• Body mass index (BMI) \>45 kg/m2.
• 6-minute walk test distance \<100 meters OR \>450 meters.
• Admission for HF within the 30 days prior to planned index procedure.
• Any known history of orthostatic hypotension or orthostatic hypotension at the time of screening (regardless of the presence of symptoms). Orthostatic hypotension is defined as a systolic blood pressure (BP) decrease of \>20 mmHg upon going from supine to standing position or undergoing treatment with Midodrine.
• Orthostatic pulse pressure change from supine to standing decrease of \>10mmHg in the absence of a HR increase \>15bpm
• Postural orthostatic tachycardia syndrome or preload insufficiency syndrome.
• Systolic BP \<100 mmHg or \>170 mmHg despite appropriate medical management.
• Baseline screening ECG resting HR \>100 beats per minute or ventricular tachycardia.
• Catheter ablation for atrial fibrillation within 6 months prior to screening or planned in the next 12 months at the time of screening.
• Left ventricular EF \<40% within the 3 years prior to screening unless reduced EF was transient and associated with an acute event.
• Presence of significant valve disease defined by the site cardiologist as:
• Greater than mild mitral valve stenosis.
• Greater than moderate mitral valve regurgitation.
• Greater than moderate-to-severe tricuspid valve regurgitation.
• Greater than moderate aortic valve stenosis or regurgitation.
• Known hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis).
• History of clinically significant liver cirrhosis.
• Prior weight loss surgery
• Dialysis dependent; or estimated GFR \<25 ml/min/1.73 m2 by CKD-EPI creatinine equation.
• Arterial oxygen saturation \<90% on room air.
• Chronic pulmonary disease requiring continuous home oxygen OR hospitalization for exacerbation of chronic pulmonary disease (including intubation) in the 12 months before study entry OR known history of GOLD Class III or worse chronic obstructive pulmonary disease (COPD).
• Participating in conflicting investigational drug or device study that is not completed within 30 days prior to the screening visit.
• Life expectancy \<12 months for non-cardiovascular reasons.
• Any condition, or history of illness or surgery that, in the opinion of the site investigator or Screening Committee, might confound the results of the study or pose additional risks to the patient.
• Females who are pregnant or lactating or planning to become pregnant during the next year.
• Any of the following measured by screening right heart catheterization:
• Mean right atrial pressure (RAP) \>20 mmHg at rest
• Cardiac index \<2.0 L/min/m2 at rest
• Pulmonary vascular resistance (PVR) \>4 Wood units Exclusion Criteria Assessed During the index procedure:
• Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the interventional device from the access site to target vessel. This includes previous spine surgery that may impact the ability to access and treat the target sites of T11 and T10.
• Chronic heart failure, defined as:
• Symptoms of HF requiring current (intermittent or continuous) treatment with diuretics for \>30 days, AND
• NYHA class II with a history of \>NYHA class II in the past year, NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening or signs of HF (any rales post cough, chest x-ray demonstrating pulmonary congestion), AND
• At least one of the following: i. ≥1 HF hospital admission (with HF as the primary diagnosis) including treatment with intravenous (IV) diuretics or urgent unplanned treatment with IV diuretics in healthcare facility within past 12 months, OR ii. NT-proBNP \>300 pg/ml in normal sinus rhythm (\>450 pg/ml in atrial fibrillation or flutter) within the past 6 months; BNP \>100 pg/ml in normal sinus rhythm (\>300 pg/ml in atrial fibrillation or flutter) within the past 6 months, OR iii. Right heart catheterization (RHC) with PCWP ≥ with PCWP ≥18 mmHg at rest or 25 mmHg during exercise at the time of the screening RHC.
• Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2022 ACCF/AHA Guideline for the Management of Heart Failure (Class 1 and 2a recommendations), with no significant changes \[≥100% increase or ≥50% decrease\] for a minimum of 1 month (30 days) prior to screening, that is expected to be maintained without change for at least 6 months. Participants cannot have started a glucagon-like peptide (GLP)-1 or gastric inhibitory peptide (GIP) agonist within the last 6 months or plan to start a GLP-1 or GIP agonist within the ensuing 6 months after enrollment.
• LVEF ≥50% (site-determined by transthoracic echocardiography) within the past 6 months.
• Age ≥40 years.
• Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.
Exclusion Criteria:
• MI (type I) and/or percutaneous cardiac intervention within 3 months prior to screening; CABG in past 3 months prior to screening, or current indication for coronary revascularization.
• Cardiac resynchronization therapy initiated within 3 months prior to screening.
• Advanced heart failure defined as one or more of the following:
• ACC/AHA/ESC Stage D HF or non-ambulatory NYHA Class IV HF.
• Inotropic infusion (continuous or intermittent) within 6 months prior to screening.
• Subject is on the cardiac transplant waiting list.
• Presence of or prior history of mechanical circulatory support for HF.
• Poor left heart compliance as determined by pulse-wave Doppler transmitral early-to-late (E/A) ratio \>2.0 assessed by the screening echocardiogram. The Screening Committee will evaluate left heart function if the transmitral A velocity is not measurable or absent.
• Right heart dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) \<12 mm or right ventricular (RV) fractional area change (FAC) \<25% assessed by the screening echocardiogram.
• Body mass index (BMI) \>45 kg/m2.
• 6-minute walk test distance \<100 meters OR \>450 meters.
• Admission for HF within the 30 days prior to planned index procedure.
• Any known history of orthostatic hypotension or orthostatic hypotension at the time of screening (regardless of the presence of symptoms). Orthostatic hypotension is defined as a systolic blood pressure (BP) decrease of \>20 mmHg upon going from supine to standing position or undergoing treatment with Midodrine.
• Orthostatic pulse pressure change from supine to standing decrease of \>10mmHg in the absence of a HR increase \>15bpm
• Postural orthostatic tachycardia syndrome or preload insufficiency syndrome.
• Systolic BP \<100 mmHg or \>170 mmHg despite appropriate medical management.
• Baseline screening ECG resting HR \>100 beats per minute or ventricular tachycardia.
• Catheter ablation for atrial fibrillation within 6 months prior to screening or planned in the next 12 months at the time of screening.
• Left ventricular EF \<40% within the 3 years prior to screening unless reduced EF was transient and associated with an acute event.
• Presence of significant valve disease defined by the site cardiologist as:
• Greater than mild mitral valve stenosis.
• Greater than moderate mitral valve regurgitation.
• Greater than moderate-to-severe tricuspid valve regurgitation.
• Greater than moderate aortic valve stenosis or regurgitation.
• Known hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis).
• History of clinically significant liver cirrhosis.
• Prior weight loss surgery
• Dialysis dependent; or estimated GFR \<25 ml/min/1.73 m2 by CKD-EPI creatinine equation.
• Arterial oxygen saturation \<90% on room air.
• Chronic pulmonary disease requiring continuous home oxygen OR hospitalization for exacerbation of chronic pulmonary disease (including intubation) in the 12 months before study entry OR known history of GOLD Class III or worse chronic obstructive pulmonary disease (COPD).
• Participating in conflicting investigational drug or device study that is not completed within 30 days prior to the screening visit.
• Life expectancy \<12 months for non-cardiovascular reasons.
• Any condition, or history of illness or surgery that, in the opinion of the site investigator or Screening Committee, might confound the results of the study or pose additional risks to the patient.
• Females who are pregnant or lactating or planning to become pregnant during the next year.
• Any of the following measured by screening right heart catheterization:
• Mean right atrial pressure (RAP) \>20 mmHg at rest
• Cardiac index \<2.0 L/min/m2 at rest
• Pulmonary vascular resistance (PVR) \>4 Wood units Exclusion Criteria Assessed During the index procedure:
• Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the interventional device from the access site to target vessel. This includes previous spine surgery that may impact the ability to access and treat the target sites of T11 and T10.
DEVICE: Greater Splanchnic Nerve Ablation, DEVICE: Sham Control
Heart Failure With Preserved Ejection Fraction (HFpEF
Heart Failure with Preserved Ejection Fraction (HFpEF), HFpEF, Greater Splanchnic Nerve, GSN
SynCardia 70cc TAH-t for Destination Therapy (DT) (RA-540)
Judy Skroback, CIP, CRCP - jskroback@syncardia.com
Medalion, Benjamin
NCT02232659
HM20004553
Primary Arm
• Patients with ife-threatening, irreversible biventricular heart failure (Intermacs Patient Profile Classifications 1 - 4)
• Ineligible for cardiac transplantation (e.g., contraindication to immunosuppression, cancer, elevated panel reactive antibodies [PRAs]) as determined by the implanting center at time of implant screening assessment.
• On optimal medical management and failing to respond or failing DT VAD therapy (continuing to decline)
• Ambulatory without assistance
• Patients between 19 and 75 years of age
• Patients with Body Surface Area (BSA) of ? 1.7m2
• Sternum to T10 distance > 10cm OR adequate room in chest as determined by 3-D imaging assessment or by other standard clinical assessments
• Cardiac transplant-eligible patients
• Patients who cannot be adequately anticoagulated on the TAH-t
• Patients with insufficient space in the chest
• Patients on ECMO support
• Patients with Cirrhosis (evidenced by ultrasound, CT scan, or positive biopsy)
• Patients with Acute or Chronic Renal dysfunction (per Intermacs AE Definitions)
• Patients with cardiac cachexia (e.g., pre-albumin <17, fragility, and catabolic/anabolic imbalance)
• Patients with a comorbidity that has a poor prognosis of survival beyond six months
• Patients with insufficient social support or who have demonstrated non-compliance with medical instructions (as determined by the Principal Investigator) Secondary Arm
• Patients who are NOT eligible to participate in the Primary Arm
• Patients with life-threatening, irreversible biventricular heart failure (Intermacs Patient Profile Classifications 1 - 7)
• Ineligible for cardiac transplantation (as determined by the implanting center at time of implant screening assessment).
• On optimal medical management and failing to respond or failing DT VAD therapy (continuing to decline)
• Patients 19 years of age or older
• Sternum to T10 distance > 10cm OR adequate room in chest as determined by 3-D imaging assessment or by other standard clinical assessments
• Patients who are less than 19 years old
• Cardiac transplant-eligible patients
• Patients with Cirrhosis (evidenced by ultrasound, CT scan, or positive biopsy)
• Patients with Chronic Renal dysfunction (per Intermacs AE Definitions)
• Patients with insufficient space in the chest
• Patients who cannot be adequately anticoagulated on the TAH-t
• Patients with insufficient social support or who have demonstrated non-compliance with medical instructions (as determined by the Principal Investigator)
Inclusion Criteria:
• Patients with ife-threatening, irreversible biventricular heart failure (Intermacs Patient Profile Classifications 1 - 4)
• Ineligible for cardiac transplantation (e.g., contraindication to immunosuppression, cancer, elevated panel reactive antibodies [PRAs]) as determined by the implanting center at time of implant screening assessment.
• On optimal medical management and failing to respond or failing DT VAD therapy (continuing to decline)
• Ambulatory without assistance
• Patients between 19 and 75 years of age
• Patients with Body Surface Area (BSA) of ? 1.7m2
• Sternum to T10 distance > 10cm OR adequate room in chest as determined by 3-D imaging assessment or by other standard clinical assessments
Exclusion Criteria:
• Cardiac transplant-eligible patients
• Patients who cannot be adequately anticoagulated on the TAH-t
• Patients with insufficient space in the chest
• Patients on ECMO support
• Patients with Cirrhosis (evidenced by ultrasound, CT scan, or positive biopsy)
• Patients with Acute or Chronic Renal dysfunction (per Intermacs AE Definitions)
• Patients with cardiac cachexia (e.g., pre-albumin <17, fragility, and catabolic/anabolic imbalance)
• Patients with a comorbidity that has a poor prognosis of survival beyond six months
• Patients with insufficient social support or who have demonstrated non-compliance with medical instructions (as determined by the Principal Investigator) Secondary Arm
Inclusion Criteria:
• Patients who are NOT eligible to participate in the Primary Arm
• Patients with life-threatening, irreversible biventricular heart failure (Intermacs Patient Profile Classifications 1 - 7)
• Ineligible for cardiac transplantation (as determined by the implanting center at time of implant screening assessment).
• On optimal medical management and failing to respond or failing DT VAD therapy (continuing to decline)
• Patients 19 years of age or older
• Sternum to T10 distance > 10cm OR adequate room in chest as determined by 3-D imaging assessment or by other standard clinical assessments
Exclusion Criteria:
• Patients who are less than 19 years old
• Cardiac transplant-eligible patients
• Patients with Cirrhosis (evidenced by ultrasound, CT scan, or positive biopsy)
• Patients with Chronic Renal dysfunction (per Intermacs AE Definitions)
• Patients with insufficient space in the chest
• Patients who cannot be adequately anticoagulated on the TAH-t
• Patients with insufficient social support or who have demonstrated non-compliance with medical instructions (as determined by the Principal Investigator)
Device: 70cc TAH-t for Destination Therapy
Life-threatening, Biventricular Heart Failure, Ineligible for Cardiac Transplant
SynCardia, Total Artificial Heart, Biventricular heart failure, Ineligible for cardiac transplant
Cardiac Resynchronization Therapy Delivery Guided Non-Invasive Electrical and Venous Anatomy Assessment (CRT-DRIVE)
Claudia M Amatruda, PhD - amatruda@xspline.com
NCT05327062
Eligible subjects shall meet all following criteria:
• Appropriately signed and dated informed consent.
• Age ≥18 years at time of consent.
• CRT indication according to the 2021 ESC guidelines on cardiac pacing and CRT (class I and IIA indication in patients with LBBB QRS morphology) or to 2017 AHA/ACC/HFSA guidelines (COR I).
• Sinus rhythm
• QRS duration ≥130 ms
• Left bundle branch block
• Left ventricular ejection fraction ≤35%
• Symptomatic heart failure NYHA class ≥ II
• Documented stable medical treatment for at least 6 months
• No cardiovascular intervention during the last 6 month Exclusion Criteria are:
• History of persistent or permanent atrial fibrillation
• Previous pacemaker or ICD implantation
• Indication to pacing due to bradycardia
• Patients considered for His bundle pacing or cardiac conduction pacing
• Patients with unstable angina
• Subject experienced a recent myocardial infarction, within 40 days prior to enrollment
• Subject underwent coronary artery bypass graft or valve surgery, within 90 days prior to enrollment
• Subject is post heart transplantation, or is actively listed on the transplantation list, or has reasonable probability (per investigator's discretion) of undergoing transplantation in the next year
• Subject is implanted with a left ventricular assist device
• Subject is on continuous or uninterrupted infusion (inotropic) therapy for heart failure
• Subject has severe aortic stenosis (with a valve area of <1.0 cm2 or significant valve disease expected to be operated within study period)
• Subject has congenital heart disease
• Subject has a mechanical right-sided heart valve
• Subject has a life expectancy of less than one year in the opinion of the investigator
• Pregnant or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth control
• Subject is enrolled in one or more concurrent studies that would confound the results of this study
• Patients who have contraindications to CT scanning.
• Patients with chronic kidney diseases and estimated glomerular filtration rate (eGMR) calculated based on CKD-EPI 2009 < 40 ml/min/1.73m2
• Appropriately signed and dated informed consent.
• Age ≥18 years at time of consent.
• CRT indication according to the 2021 ESC guidelines on cardiac pacing and CRT (class I and IIA indication in patients with LBBB QRS morphology) or to 2017 AHA/ACC/HFSA guidelines (COR I).
• Sinus rhythm
• QRS duration ≥130 ms
• Left bundle branch block
• Left ventricular ejection fraction ≤35%
• Symptomatic heart failure NYHA class ≥ II
• Documented stable medical treatment for at least 6 months
• No cardiovascular intervention during the last 6 month Exclusion Criteria are:
• History of persistent or permanent atrial fibrillation
• Previous pacemaker or ICD implantation
• Indication to pacing due to bradycardia
• Patients considered for His bundle pacing or cardiac conduction pacing
• Patients with unstable angina
• Subject experienced a recent myocardial infarction, within 40 days prior to enrollment
• Subject underwent coronary artery bypass graft or valve surgery, within 90 days prior to enrollment
• Subject is post heart transplantation, or is actively listed on the transplantation list, or has reasonable probability (per investigator's discretion) of undergoing transplantation in the next year
• Subject is implanted with a left ventricular assist device
• Subject is on continuous or uninterrupted infusion (inotropic) therapy for heart failure
• Subject has severe aortic stenosis (with a valve area of <1.0 cm2 or significant valve disease expected to be operated within study period)
• Subject has congenital heart disease
• Subject has a mechanical right-sided heart valve
• Subject has a life expectancy of less than one year in the opinion of the investigator
• Pregnant or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth control
• Subject is enrolled in one or more concurrent studies that would confound the results of this study
• Patients who have contraindications to CT scanning.
• Patients with chronic kidney diseases and estimated glomerular filtration rate (eGMR) calculated based on CKD-EPI 2009 < 40 ml/min/1.73m2
Device: CRT implantation guided by XSpline, a non-invasive electrical and venous anatomy assessment
Cardiac Resynchronization Therapy, Chronic Heart Failure, Left Bundle-Branch Block
Non-invasive activation mapping, Coronary Sinus
Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator (CARVTOP-ICD)
Mehmet Aktas, M.D. - Mehmet_Aktas@URMC.Rochester.edu
NCT06964464
Inclusion Criteria:
* Age ≥ 18 years
* ICD implanted for primary prevention for HFrEF (either ICM or NICM) with remote monitoring capability
* Current treatment with metoprolol succinate and willing to switch to carvedilol
* LVEF \<50% during the past 12 months prior to consent
Exclusion Criteria:
* Unwilling or unable to follow the protocol
* Treatment with any other ßB than metoprolol succinate or no ßB treatment
* Known prior intolerance or contraindication to carvedilol
* Systolic blood pressure \<100 mmHg
* Enrollment in another clinical trial
* Inability or unwilling to consent DRUG: Metoprolol Succinate, DRUG: Carvedilol
Heart Failure With Reduced Ejection Fraction (HFrEF), Sudden Cardiac Death, Ventricular Arrhythmia, Implantable Cardioverter Defibrillator (ICD), Beta-blocker Therapy, Cardiomyopathy
arrhythmia, heart failure, ICD, implantable cardioverter defibrillator, ICD shock, carvedilol, metoprolol succinate, beta-blocker
A Prospective Registry Study to Assess Real-world Patient Characteristics, Treatment Patterns, and Longitudinal Outcomes in Patients Receiving Mavacamten and Other Treatments for Symptomatic Obstructive Hypertrophic Cardiomyopathy (Obstructive-HCM) (DISCOVER-HCM)
BMS Study Connect Contact Center www.BMSStudyConnect.com - Clinical.Trials@bms.com
NCT05489705
Inclusion Criteria
* ≥ 18 years of age at the time of informed consent.
* Willing and able to provide written informed consent form (ICF) and any required privacy authorization prior to the initiation of study procedures (or in those situations where consent cannot be given by participants, consent provided by their legally acceptable representatives)
United States Sub-Study
* Diagnosis of obstructive HCM consistent with 2020 American Heart Association/American College of Cardiology (AHA/ACC) guidelines.
* Obstructive HCM is defined clinically by the presence of increased LV wall thickness ≥ 15 mm (or ≥ 13 mm with positive family history of HCM) in a nondilated ventricular chamber that is not solely explained by abnormal loading conditions (eg, another cardiac or systemic disease) and peak LVOT gradient of ≥ 30 mmHg at rest or with provocation.
* Has documented LVEF of ≥ 55% recorded by echocardiography within the last 6 months.
* Symptoms consistent with NYHA functional class II-IV.
* Receiving beta blocker (BB)s, non-dihydropyridine calcium. channel blockers (nonDHP CCBs), disopyramide, and/or mavacamten (once available) as part of routine clinical care; or currently receiving no treatment due to intolerance or failure of prior treatment (eg, BBs, non-DHP CCBs, or disopyramide) for obstructive HCM.
European Sub-study
* Diagnosis of obstructive HCM consistent with the most recent European Society of Cardiology (ESC) and American Heart Association/American College of Cardiology (AHA/ACC) guidelines
* Documented LVEF of ≥55% recorded by TTE
* Documented symptoms consistent with NYHA functional class II-III at enrollment or within 6 months prior to enrollment (if not available at enrollment).
* As part of routine clinical care for obstructive HCM: receiving BBs, non-DHP CCBs, disopyramide; initiating mavacamten at enrollment; or currently receiving no treatment due to intolerance or failure of prior treatment (e.g., BBs, non-DHP CCBs, or disopyramide).
Exclusion Criteria
* Known phenocopy disease (e.g., Fabry disease, amyloidosis) or LV hypertrophy associated with hypertension.
* Documentation of any fixed obstruction of the outflow tract such as aortic valve stenosis or replacement.
* Prior treatment of obstructive HCM with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation \[ASA\]) within 6 months prior to enrollment; participants with an unsuccessful myectomy or percutaneous ASA performed \> 6 months prior to enrollment may be enrolled.
* Naïve to treatment for obstructive HCM (ie, never treated with BBs, nonDHP CCBs, or disopyramide).
United States Sub-Study
* Receiving an investigational therapeutic agent for obstructive HCM (eg, myosin-inhibitors other than mavacamten) in an interventional clinical trial at participant enrollment.
* Previously or currently enrolled in a long-term safety extension study of mavacamten (eg, EXPLORER-HCM \[ClinicalTrials.gov, NCT03470545\], MAVA-LTE \[NCT03723655\], PIONEER-OLE \[NCT03496168\], VALORHCM \[NCT04349072\], or MAVERICK \[NCT03442764\])
European Sub-study
* Receiving an investigational therapeutic agent or any cardiac myosin inhibitor and/or modulators for obstructive HCM at patient enrolment
* Previously or currently enrolled in other HCM registry studies (e.g., TORCH, REMY, EU-PASS)
* Previously or currently enrolled in a study of mavacamten (e.g., EXPLORER-HCM \[ClinicalTrials.gov, NCT03470545\], MAVA-LTE \[NCT03723655\], PIONEER-OLE \[NCT03496168\], VALOR-HCM \[NCT04349072\], MAVERICK \[NCT03442764\], or MEMENTO \[NCT2264899\])
* Previously treated with mavacamten
DRUG: Mavacamten, DRUG: Non-mavacamten symptomatic oHCM therapy
Obstructive Hypertrophic Cardiomyopathy
Obstructive hypertrophic cardiomyopathy, Obstructive HCM (oHCM), Mavacamten, Heart failure, oHCM
MYTHS - MYocarditis THerapy With Steroids (MYTHS)
Enrico Ammirati, MD, PhD - enrico.ammirati@ospedaleniguarda.it
NCT05150704
Inclusion Criteria:
* Patients admitted to hospital for suspected AM
* Age 18 years or older and below 70 years (18-69 years)
* Acute HF with clinically suspected acute myocarditis based on an N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration of 1600 pg/mL or more or a B-type natriuretic peptide (BNP) concentration of 400 pg/mL or more;
* Left ventricular ejection fraction (LVEF)\<41% and left ventricular end diastolic diameter (LV-EDD)\<56 mm (parasternal long-axis view) on echocardiogram;
* Increased troponin (3x upper reference limit \[URL\]) at the time of randomization;
* Clinical onset of cardiac symptoms within 3 weeks from randomization;
* Excluded coronary artery disease by coronary angiogram in subjects ≥46 years of age, in case myocarditis is not histologically proven;
* Randomization within 120 hours from hospital admission.
Exclusion Criteria:
* Known systemic autoimmune disorder or other conditions at the time of randomization where immunosuppression is assumed useful. Patients in whom a systemic autoimmune disorder will be diagnosed during hospitalization will be included in the study if randomized, including patients with a diagnosis of cardiac sarcoidosis or giant cell myocarditis (GCM). Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis of a systemic autoimmune disorder, or cardiac sarcoidosis or GCM;
* Patients already on oral/IV chronic corticosteroid therapy or other chronic immunosuppressive therapies (colchicine or nonsteroidal anti-inflammatory drugs \[NSAIDs\] are not considered immunosuppressive drugs);
* Contraindication to corticosteroids, including allergies to this medication and its excipients;
* Patients with persistent peripheral eosinophilia (persistent Eosinophil count \>7% of the leukocytes) or known hypereosinophilic syndrome at the time of randomization. Patients in whom eosinophilic myocarditis will be diagnosed on endomyocardial biopsy (EMB) will be included in the study if already randomized. Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis;
* Myocarditis associated with the ongoing administration of anti-cancer immune checkpoint inhibitor (ICI) agents;
* Previously known chronic cardiac disease (i.e., previous cardiomyopathy) that does NOT include previous myocarditis if there is a functional recovery at the time of screening);
* Evidence of active bacterial or fungal infectious disease (presence of fever or increased C-reactive protein are not considered exclusion criteria), or suspected bacterial/fungal infection associated with increased levels of procalcitonin (cut-off \>10 ng/mL), if the laboratory exam is available in the center;
* Known chronic infective disease, such as HIV infection or tuberculosis;
* out-of-hospital cardiac arrest;
* t-MCS instituted more than 48 hours before randomization;
* Patients clinically judged too sick to initiate t-MCS (i.e., irreversible multiorgan failure);
* Echocardiographic presence of images suggestive of other cardiac diseases (i.e. endocarditis)
* Participants involved in another clinical trial;
* Pregnant women (known pregnancy) or POSITIVE human chorionic gonadotropin (HCG) test measures (urine/blood) for women of 18-50 years of age.
* Any other significant disease with expected life expectancy \<12 months (i.e., evidence of irreversible severe brain injury) or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial. DRUG: Methylprednisolone, DRUG: saline solution
Myocarditis Acute
Acute Myocarditis, Corticosteroid therapy, Myocarditis, Trial, Immunosuppression, Acute heart failure, Fulminant acute myocarditis
CLEOPATTRA: A Research Study to Look at the Effects of Treatment With a Medicine Called Coramitug (NNC6019-0001) in People With Heart Failure Due to Transthyretin Amyloid (ATTR) Amyloidosis (CLEOPATTRA)
Novo Nordisk - clinicaltrials@novonordisk.com
NCT07207811
Inclusion Criteria:
* Male or female.
* Age 18 years or above at the time of signing the informed consent.
* Have an established diagnosis of ATTR-CM (wild-type ATTR \[ATTRwt\] or variant ATTR \[ATTRv\]), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF.
Note: Target ATTRv recruitment is approximately 15 percent of the study population.
• Cardiac amyloid infiltration demonstrated by: * Cardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) nuclear medicine imaging with single-photon emission computed tomography (SPECT) or SPECT/CT (preferably) combined with an extracardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP nuclear medicine imaging with SPECT or SPECT/CT (preferably) combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE)/or mass spectrometry based methods including mass fixation). Notes: * Non-invasive diagnostic pathway will be confirmed by a centralised expert review. * Bone tracer nuclear medicine imaging with SPECT or SPECT/CT (preferably) will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP). * The eGFR adjusted acceptable serum free light chain ratio. * Patients with Grade 2 or 3 cardiac uptake at PYP/DPD/HDMP nuclear imaging with SPECT or SPECT/CT (preferably) and evidence of monoclonal gammopathy of undetermined significance (MGUS; based on serum and urine protein electrophoresis and serum free light chains) will require endomyocardial biopsy with typing using mass spectrometry or immunohistochemistry to confirm presence of TTR protein in tissue. * Timing of serum free light chain ratio, SPIE, UPIE and mass spectrometry-based methods including mass fixation should be within 12 months of SPECT or SPECT/CT nuclear imaging.
• Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm).
• Chronic HF (New York Heart Association \[NYHA\] Class I-IV): * At least 1 documented hospitalisation for HF, OR * History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema that required or requires ongoing treatment with a diuretic). * Expected to be on stable cardiovascular medical therapy (defined as no greater than 50 percent dose adjustment and no categorical changes of medications), with the exception of diuretics, 4 weeks prior to the randomisation visit. * Completed more than 50 meters on the 6MWT at screening.
Exclusion Criteria:
* Known or suspected hypersensitivity to study intervention(s) or related products.
* Current or previous participation (dosing with active treatment) in a study for an investigational ATTR depleting drug or ATTR gene editing therapy.
* Total bilirubin greater than 3 times the upper limit of normal (ULN) at screening.
* Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis, known leptomeningeal amyloidosis, or multiple myeloma.
* HF not primarily caused by ATTR-CM (e.g., due to hypertension, valvular heart disease, or ischemic heart disease in the opinion of the investigator).
* Currently hospitalised or hospitalised within 14 days prior to screening.
* Currently treated with positive inotropic medication.
* Uncorrected, severe, haemodynamically significant, left-sided heart valve disease.
* Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 60 days of screening.
* Prior solid organ transplant or planned solid organ transplant during the study.
* Left ventricular ejection fraction (LVEF) less than 30 percent as assessed by centralised review of echocardiography.
* Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, carcinoma in situ/high-grade prostatic intraepithelial neoplasia \[PIN\], low-risk prostate cancer, or on stable therapy for prostate cancer) within 3 years before screening.
* End-stage renal disease (estimated glomerular filtration rate \[eGFR\] less than 15 mL/min/1.73 m\^2 at screening, or chronic/intermittent haemodialysis or peritoneal dialysis). DRUG: NNC6019-0001, DRUG: Placebo (NNC6019-0001)
Transthyretin Amyloid Cardiomyopathy (ATTR CM)
Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia (ORION-20)
Novartis Pharmaceuticals - novartis.email@novartis.com
NCT06597019
Inclusion Criteria:
* Male or female participants, 6 to \<12 years of age at screening
* HeFH diagnosed either by genetic testing or on phenotypic criteria
* Fasting LDL-C \>130 mg/dL (3.4 mmol/L) at screening
* For participants 8 to \<12 years, on an optimal dose of statin (investigator's discretion) unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe). For participants \<8 years, the use of background lipid-lowering treatment is based on investigator's discretion.
* Participants on lipid-lowering therapies (such as statin and/or e.g. ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation.
Exclusion Criteria:
* Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
* Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
* Homozygous familial hypercholesterolemia (HoFH)
* Body weight \<16 kg at the screening and/or randomization (Day 1) visit
* Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation \>3x ULN, or total bilirubin elevation \>2x ULN (except patients with Gilbert's syndrome)
* Pregnant or nursing females
* Recent and/or planned use of other investigational medicinal products or devices DRUG: Inclisiran, DRUG: Placebo
Familial Hypercholesterolemia - Heterozygous
Heterozygous familial hypercholesterolemia (HeFH),, LDL-cholesterol (LDL-C),, Children,, pediatric,, small interfering ribonucleic acid (siRNA),, inclisiran,, Familial Hypercholesterolemia,, Heterozygous FH,, Hypercholesterolemia,, Lipoprotein(a),, Hyperlipidemia,, Dyslipidemia,, Heart Failure,, Cardiovascular Diseases,, Cholesterol,, Aortic Stenosis