Other / Invasive / Experimental / Hospice:
Links: Biventricular Pacing / Resynchronization (CRT) | Enhanced External Counterpulsation (ECP), Assist Device, Infusions, Ultrafiltration and Other | Heart Transplantation | Intra-aortic Balloon Pump (IABP) | Class / Stage / Prognosis |
Consider pulmonary artery catheter placement to guide therapy in pt’s with persistently severe sx’s. Low-level leg exercise (bicycle and treadmill and leg calisthenics ) improves dyspnea in pt’s with severe CHF (J Am Coll Cardiol 2002;40:1602-1608). Pentoxifylline may be a useful adjunctive therapy (inhibits TNF-alpha) in pt’s with severe heart failure as improves left ejection fraction (Am J Cardiol 2002;90:1118-1122). It is feasible to treat pt’s with end-stage heart failure at home with continuous inotropic therapy (via Hickman catheter), both as a destination therapy in itself and as a bridge to heart transplant (Int J Cardiol 2005;99:47-50).
Other:
Biventricular (atrial synchronized) Pacing: Implant a “cardiac-resynchronization (CR)” therapy (CRT) device with 3 lead pacing (standard R atrial lead, standard R vent lead and a specialized L ventricular lead).
Indications for BiV implantation: irreversible symptomatic heart failure for at least six mo’s, NYHA class III or IV, LF ejection fraction <35%, and QRS duration of 150 ms or more. FDA approved for pt’s with moderate CHF despite optimal medical therapy and with significant intraventricular conduction delay. The onset of LV contraction is optimal if occurs with <40 ms of variation throughout the wall, otherwise get a disorganized contraction (asynergy). Resynchronization therapy for symptomatic (NYHA class 3 or 4) dilated/ hypertrophic cardiomyopathy (EF <35%), particularly useful if have LBBB or an intraventricular conduction delay (QRS >120 msec or prolonged PR interval) to improve the synchronization of the contraction & relaxation to improve EF & sx’s (Mayo Clin Proc 2001;76:803).
• Reduces death or worsening CHF and improves quality of life in pt’s with mod-severe heart failure and an intraventricular conduction delay (NEJM 2002;346:1845-53).
• Cardiac resynchronization may reverse LV remodeling (Circulation 2003;107:1985-1990). Pt’s with implantable cardioverter defibrillators (ICD) for the tx of chronic heart failure showed improved functional status, quality of life scores, and exercise capacity when also receiving CRT through biventricular pacing (JAMA 2003;289:20:2685-2694). Cardiac resynchronization therapy and ICDs improve survival in pt’s with ischemic cardiomyopathy and prolonged QRS interval (>120 ms) (NEJM 2004;350:2140-2150, 2151-8).
• CRT reduces mortality and hospitalizations for heart failure at a rate similar to that achieved with medical therapy alone (Ann Intern Med 2004;343-351,391-400,409-410) CRT costs twice as much as meds ($64,400 per quality-adjusted life year = QALY Vs $34,400), can be considered in pt’s with heart failure, an EF <35%, and a QRS duration >120 ms who remain symptomatic despite meticulous fluid management and drug therapy. In 10/04 Medicare expanded coverage to include pt’s with ischemic dilated cardiomyopathy and a history of myocardial infarction as well as those with nonischemic dilated cardiomyopathy of > 9 mo’s’ duration and in addition, it eliminates QRS duration as a coverage criterion. The use of microvolt T-wave alternans (MTWA) testing can effectively predict pt’s that are likely and unlikely to benefit from ICD prophylactic therapy as it is strongly correlated with an increased risk of reentrant ventricular tachyarrhythmias and sudden cardiac death (Circulation. 2004;110:1885-1889).
• As many as 30% of pt’s tx with CRT do not respond to tx, positioning the LV lead in the lateral and posterolateral sites of the left ventricle significantly improves LV function compared with the anterior and anterolateral sites (J Cardiovasc Electrophysiol. 2004;14:1120-1125). Adding an implantable cardiac biventricular resychronization device to optimal medical therapy has such a robust effect on improving heart function and reducing mortality in advanced heart failure (NEJM 2005;352:1539-49) (at 30 mo’s, deaths in 20% in the resynchronization arm Vs 30% in the “usual medical therapy” arm). The amount of QRS shortening associated with biventricular stimulation appears to be the only independent predictor of a positive response to cardiac resynchronization therapy in pt’s with refractory CHF (Eur Heart J 2005;26:1094-1100).
• V-V timing (adjusting the RV and LV intracardiac electrogram timing) measurement can guide the implanter toward a more optimum pacing site and increase responders to CRT (Heart Rhythm. 2006;3(1S):S99). Acute cardiac resynchronization therapy reduces functional MR at rest and during physical exercise in chronic heart failure pt’s with LV systolic dysfunction (Heart 2006;92:1091-1095). The pacing site with the maximal cardiac index is “highly variable” from pt to pt, a finding which is significant when a pt with heart failure is being considered for biventricular pacing (Heart 2006;92:1795-1800). In pt’s with advanced heart failure, the level of BNP before pacemaker implantation predicts the response to cardiac resynchronization therapy (Am J Cardiol 2007;99:242-246)…. A preimplantation BNP value of 447 pg/mL or greater had a specificity of 79% and a sensitivity of 62% in predicting CRT response.
• The use of CRT, either with or without defibrillator backup, in pt’s with NYHA class 4 heart failure, can help them live and stay out of the hospital longer, and, contrary to some concerns, the implantation procedure doesn’t seem to put them at special risk (Circulation. 2007; 115:204–212). Pt’s with advanced heart failure and ventricular function delay (QRS duration of 120 ms or greater) who are treated with cardiac resynchronization therapy have a favorable long-term outcome (Am J Cardiol 2007;99:232-238).
• Under the right circumstances, CRT can benefit pt’s with CHF who are in AF as much as those in sinus rhythm (Am J Cardiol 2007; DOI:10.1016/j.amjcard.2006.12.040)….If after 3 to 6 months the pacing is inadequate, a His-bundle ablation should very seriously be considered……because of the significant chance that a pt in AF will revert to sinus rhythm, placement of an atrial lead at the time of device implantation should be strongly considered for pt’s in whom the duration of AF is <2 years. Cardiac resynchronization therapy can be effective in pt’s with advanced inotrope-dependent end-stage heart failure (Am J Cardiol 2007;100:90-93). Cardiac resynchronization therapy may not benefit about a quarter of the country’s estimated 500,000 heart failure pt’s who have normal QRS (<120 milliseconds)…..In pt’s with moderate heart failure (EF <35%) involving mechanical dyssynchrony and a narrow QRS interval (< 130 msec), CRT does not improve peak oxygen consumption on exercise testing (NEJM 2007;357:2461-2471)…..in the subgroup of pt’s with a QRS interval of 120 msec to 130 msec, CRT was associated with a significant improvement in peak oxygen consumption…..Still, their quality-of-life scores and 6-minute walking test results were unaffected. Resynchronization therapy via implanted devices can have an effect on exercise performance in heart failure patients as early as 3 months after implantation (Heart 2008;94:59-64). A study found that the presence of mechanical dyssynchrony as measured by simple Doppler echocardiography can help predict the response of heart-failure patients to CRT among those in whom the value of CRT is not clearly established (Eur J Heart Fail 2008; 10:273-280)…..The success rate in the group with no evidence of dyssynchrony (42%) was similar to that seen in the RethinQ study.
• CRT in heart failure patients reverses ventricular remodeling and thereby reduces ventricular arrhythmias according to data from 398 patients implanted with a combined cardiac resynchronization-defibrillator device (CRT-D) (J Am Coll Cardiol 2008;52:1442-1449). Ventricular remodeling responses and clinical outcomes with CRT in heart failure may be frustratingly variable from patient to patient, but if short-term reverse remodeling is pronounced after six months, at least there is a good chance that long-term survival will be excellent (J Am Coll Cardiol 2009;53:483-490)…..Similarly, long-term survival may be disappointing if the short-term reverse-remodeling response is poor. CRT either with or without implantable defibrillators, improves outcomes in patients with severe heart failure (HF; NYHA Class III or IV), left ventricular systolic dysfunction, and increased QRS duration as determined by electrocardiograms. Two-fifths of heart-failure patients who receive CRT aren’t benefiting clinically from the device therapy because the guidelines-specified electrocardiographic criteria for eligibility are too broad according to a meta-analysis of the major CRT trials (Arch Intern Med 2011; DOI:10.1001/archinternmed.2011.247)…….A falloff in CRT effectiveness has long been observed in patients with only moderately prolonged QRS interval…..CRT may not work when the QRS is in the 120–150 range…..”Among patients with a QRS greater than 120 ms, 40% of them have a QRS between 120 ms and 150 ms. So four out of 10 CRT devices are unnecessary.”
• The use of clinical guideline-recommended therapies for heart failure is associated with a reduced risk of mortality at two years, with the largest reduction in mortality risk observed among patients treated with cardiac resynchronization therapy (CRT) and beta blockers (J Am Heart Assoc Cardiovasc Cerebrovasc Dis 2012; DOI:10.1161/JAHA.111.000018)…..the lack of mortality benefit in patients treated with aldosterone antagonists was an unexpected finding, especially since a number of clinical trials have shown a benefit.
• Too often, heart-failure patients considered for implanted devices don’t understand the capabilities, lifestyle implications, and risks of the treatment they may be about to receive (Heart Failure Society of America 2012 Scientific Meeting; September 10, 2012; Seattle, WA. Abstract 117)…..80% “could not recall a discussion of perioperative risk or potential long-term complications, such as the publication of an advisory or recall, inappropriate shocks, or depression.
Loss of Capture in Cardiac Resynchronization Therapy: usually manifesting as worsening heart failure. The absence of both an R-S ratio of 1 in lead V1 and an R-S ratio of 1 in lead I from the 12-lead ECG detected 94% of cases of loss of LV capture. Most cases of biventricular capture (93%) were identified correctly (by the presence of at least one of the aforementioned R-S ratios) (Intern Med 2005;142:968-73).
Cardiac Resynchronization Therapy Defibrillator (CRT-D)(InSync Sentry), FDA approved in 11/04. The first device with automatic fluid monitoring that alerts pt’s and physicians to changes in thoracic cavity fluid accumulation (via changes in impedance of low-level electrical impulses), allowing prompt clinical response to changes above a preprogrammed threshold.
2008 Guidelines: Implanted Devices for Treatment of Cardiac Arrhythmias: American College of Cardiology, American Heart Association, Heart Rhythm Society (J Am Coll Cardiol 2008;51:2085)
Recommended indications for (CRT):
1. CRT now carries a Class I recommendation for the treatment of NYHA class III or ambulatory class IV heart failure in patients with LV ejection fractions <35% and QRS durations >120 ms on optimal medical treatment.
2. Class IIa indications for CRT now include patients with AF and patients dependent on ventricular pacing (provided that heart failure class and QRS duration conditions are met).
3. CRT now carries a Class IIb recommendation in patients who have NYHA class I or II heart failure, are undergoing PPM and ICD implantation, and are expected to require frequent ventricular pacing. This condition is the only indication for CRT in patients with NYHA class II or lower heart failure. Research suggests that CRT provides similar benefits to heart failure patients in atrial fibrillation or sinus rhythm (Heart 2008;94:826-827,879-883). A RCT on 610 patients suggests that CRT benefits patients with mild or asymptomatic heart failure (NYHA 1-2), clinically and in terms of reverse remodeling (most in the first 6 months), much as it benefits patients with more severe heart failure (REVERSE trial. J Am Coll Cardiol 2009; doi:10.1016/j.jacc.2009.08.011)……CRT-on patients showed a 62% reduction in risk of heart-failure hospitalization or death (p=0.003), apparently driven by the 61% reduction in risk of HF hospitalization by itself (p=0.01).
Enhanced External Counterpulsation (EECP or ECP): a noninvasive counterpart to an intra-aortic balloon pump as similar hemodynamic effect of diastolic augmentation and decreased afterload. An ECG directed “G-suit” (gravity) that sequentially squeezes the legs and hips during diastole to increase coronary perfusion (augments diastolic aortic pressure and venous return), then collapses during systole to enhance coronary flow and myocardial perfusion. 3 modified BP cuffs are wrapped around the calves, thighs and buttocks. One hour tx’s 5X/wk X 35 days (hours) to give a 78-89% improvement in functional capacity (J Am Coll Card 2003;41:379A). Also improves CHF and angina in symptomatic CAD pt’s who are not candidates for other interventions. Not good if pt has tachycardia or frequent premature beats. Data suggest that EECP can be a useful adjunct to standard therapies for pt’s with refractory angina, in whom symptomatic relief typically is difficult to achieve (J Am Coll Cardiol 2003;41:1918-25). EECP improves exercise tolerance, quality of life, and functional class in pt’s with chronic heart failure (J Am Coll Cardiol 2006;48:1198-1207).
Candidates for EECP: Pt’s with stable heart failure; NYHA class II, III (pt’s with any evidence of decompensation should not be treated until they are stable with the use of medical therapy). Pt’s with ischemic or idiopathic cardiomyopathy. Pt’s in stable condition with manageable peripheral edema. FDA approved in 1995 initially for use in stable angina, unstable angina, cardiogenic shock, and acute myocardial infarction. Pt’s with LVD (EF <35%). Pt’s with heart failure and other comorbid states that increase their surgical risks such as diabetes or pulmonary disease (Cardiology in Review 2004;12:21-25). Has emerged as a tx option for refractory angina in LV dysfunction….EECP (32, one-hour sessions over 2yrs) is an effective, durable therapeutic approach for pt’s with refractory angina and severe LV dysfunction (EF 35% or lower) (Am J Cardiol 2006;97:17-20)….52% were able to discontinue nitroglycerin use….improvements in angina sx’s and quality of life were maintained after tx in 55% at 2yrs.
Total Assist Device: Novacor/ Heart Mate. Usually as a bridge to heart transplant as only 78% last 4mo, few last 1yr. Portable devices that provide assistance to the left, right or both ventricles. Implantation of a left ventricular assist device (LVAD) can dramatically improve the survival of pt’s with advanced heart failure, especially those being treated with IV inotropic therapy (Circulation 2004;110). As of 2005, they give a 12-month survival rate of 50% (ISHLT 25th Annual Meeting: Registry Report. Presented April 7, 2005)…..78.3% received a device as a bridge to transplantation, 11.9% received a device as destination therapy. Most received a LVAD alone, some receive an LVAD and a right ventricular assist device. Chronic mechanical support with a left ventricular assist device (LVAD) confers significant survival benefit in inotrope-dependent pt’s with end-stage heart failure who are not candidates for heart transplantation (J Am Coll Cardiol 2007;50:741-747).
Continuous-flow pump: a type of surgically implanted LV assist device, is designed to improve upon the undesirable size, noise, and limited durability of pulsatile volume-displacement devices. Used in pt’s with end-stage heart disease who typically transplantation eligible and lack severe renal, pulmonary, or hepatic dysfunction, and in the absence of technical obstacles. A continuous-flow device is a viable option for pt’s awaiting heart transplantation (NEJM 2007;357:885-96)….Adverse events included bleeding requiring surgery (31%), respiratory failure (26%), sepsis (20%), ischemic stroke (6%), hemorrhagic stroke (2%), and hemolysis (3%).
Cardiac support device (CSD): slips over the heart like a snug-fitting mesh sock, several sizes available so it can be tailored to snugly fit the heart during surgery. Not trying to compress the heart, just fit the sock tightly. The CSD stretches “more longitudinally, so it changes the shape of the heart from a basketball shape — which is typical of heart failure — to a football shape, which is closer to a healthy heart. The device does not have an immediate effect, pt’s usually report improvement about 3 mo after surgery. (AHA 2004 Scientific Sessions: Presented Nov. 7, 2004). 38% of pt’s who received the support device improved while 27% of pt’s receiving standard tx improved, as measured by functional status assessment. Pt’s who received standard therapy were more likely to worsen (45%) than pt’s treated with the device (37%). An external pump to boost blood flow may not improve outcomes for patients with acute decompensated heart failure unresponsive to medical therapy (MOMENTUM trial. ACC Meeting 2008; Abstract 413-6)….the pump was successfully used for at least 24 hours in 93.4% of patients (median 94.3 hours), which consistently improved left ventricular, systemic vascular resistance, cardiac index and decreased pulmonary capillary wedge pressure by nearly 2 mm Hg….However, the device did not improve overall success in the combined primary endpoint of decreasing mean pulmonary capillary wedge pressure by at least 5 mm Hg and keeping patients alive, out of the hospital, and off mechanical support for at least 10 days without readmission for heart failure (odds ratio 1.45).
HeartPOD: by Savacor/St Jude Medical. Provides patients with the pressure readings on a handheld display module, can help them adjust their own medication dosages in response to how they feel, possibly preventing hospitalization An implantable sensor that continuously monitors left-atrial (LA) pressures in patients with heart failure, potentially warning of impending decompensation, showed that it can be safely implanted and produce reliable ambulatory LA-pressure readings in a 12-week feasibility study conducted in eight patients (Circulation 2007;116:2952-2959).
Implantable Replacement Heart (AbioCor): FDA granted a humanitarian device exemption in 9/06, allowing its use in pt’s <75 yo with severe end-stage biventricular heart failure who require multiple inotropic support, are not treatable by left-ventricular heart assist devices for destination therapy, and are not weanable from heart support measures. The pulsatile electrohydraulic device is made primarily of titanium and a proprietary polyether-based polyurethane plastic (Angioflex) and consists of 2 artificial ventricles with their corresponding valves, separated by an energy converter. The “thoracic unit” weighs ~ 2 lb and is capable of delivering blood at a rate of up to 8 L/min over a broad range of blood pressures. An implanted controller regulates and monitors the thoracic unit via wireless receipt and transmission of information to an external system thereby providing pt’s with complete mobility and remote diagnostics. In the absence of an external power source, an implanted battery can operate the system for ~ 30 minutes, allowing pt’s to conduct activities such as a shower or bath. The internal implanted battery is continually recharged via transcutaneous energy transmission to an induction coil from an external console or from a basic pt-carried external battery pack. External battery packs can power the device for ~ 4 hours, and the lack of piercing tubes and wires reduces the risk for infection. A next-generation model of the device (~ 30% smaller with a 5-year lifespan) is currently in preclinical evaluation.
Mechanical Ultrafiltration: For acute CHF. Blood is withdrawn from one vein (16g, 35mm cath in antecubital fossa), passed through the filter, and, with the aid of a pump, salt and water are removed. The excess fluid remains in a bag, and the rest of the blood goes back into the pt (via standard peripheral IV catheter). Up to 500 cc (1/2 kg or 1lb) of fluid can be removed, typically the procedure takes 8 hours. Less likely to cause electrolyte abn’s compared to diuretics. Aquadex FlexFlow system allows peripheral venous access and requires that only 33 mL of blood are extracorporeal at any given time. The cost of the device is ~$10,000-19,000, and each filter runs about $900 per session. A small tiral showed 53% reduction in the total number of hospitalizations, a 64% decrease in total hospital days, and a 53% decrease in emergency room and unscheduled office visits during the first 90 days after tx compared with diuretics (ACC 55th Annual Scientific Session: Abstract 418-7. Presented March 13, 2006). Ultrafiltration safely produces greater weight and fluid loss than IV diuretics in pt’s with hypervolemic heart failure (J Am Coll Cardiol 2007;49:675-683)….greater weight loss (5 kg versus 3.1 kg) and net fluid loss (4.6 L versus 3.3 L) than the standard-care group…..at 90 days, 18% of pt’s in the ultrafiltration group were rehospitalized for HF compared with 32% of the standard-care group. Elevated CVP was associated with poorer outcomes in pt’s with cardiorenal syndromes according to a retrospective study on 2557 patients (J Am Coll Cardiol 2009;53:582)…….elevated CVP was linked to worsening renal function and poor outcomes….likely due to the complex interactions between CVP, neurohormonal activation, and renal function in HF…….lowering CVP through mechanical means, such as ultrafiltration (rather than diuretics), might be beneficial.
Ventricular Remodeling: Batiste’s procedure, which is resection of LV muscle between the ant & post papillary muscle to reduce end-diastolic diameter and incr EF, variable results. Restoring the normal elliptical shape to the left ventricle with surgery improves cardiac function in pt’s with post-anterior infarction CHF (J Am Coll Cardiol 2004;44:1439-1445) (EF went from 29.6% preop to 39.5% postop, 5-year survival rate was 68.6%).
Transmyocardial Laser Revascularization (TMLR): uses a laser to drill small holes in the heart wall gives modest improvement in angina and ischemia for those with diffusively diseased coronary arteries. Scientists have thown that in pt’s with CAD taking part in angiogenesis and laser myocardial revascularization studies the placebo effect may be so strong and enduring that a double-blind approach is essential to achieve meaningful results (Am J Cardiol 2005;95:1456-1459).
Dynamic Cardiomyoplasty: wrapping the latissimus dorsi muscle around the heart and stimulate with a pacemaker at gradually increasing frequency over 10wks to transform type 2 fibers into type 1 muscle fibers (more aerobic & fatigue resistant), may incr EF & give functional improvement, but no incr survival or exercise capacity.
Transendocardial injection: inject autologous mononuclear bone marrow mononuclear cells in pt’s with severe heart failure is safe and may improve perfusion and function (Circulation 2003;107:3120). A RCT with 114 pt’s found no improvement in ventricular function or reduction of infarct size in the G-CSF stem cell group compared with the placebo group who had undergone successful reperfusion within 12 hours (JAMA 2006;295:1003-10). Catheter-based targeted implantation of autologous bone marrow cells into ischemic myocardium to treat severe CAD and stable angina refractory to standard medical therapy showed promise and relative lack of adverse effects in a small study with 12 pt’s (Am J Cardiol 2006;98:60-62). Injections of autologous bone marrow cells (BMC) directly into the endomyocardium of no-option patients with severe CAD improves left ventricular ejection fraction and exercise tolerance (PROTECT-CAD trial. Eur Heart J 2007;28:2998-3005). Intramyocardial injections of skeletal myoblasts in patients with ischemic cardiomyopathy does not improve ventricular function and may increase the risk of serious arrhythmia according to a Dutch in 14 patients with an average follow-up of 4 years (Eur Heart J 2008;29:1386-1396).
Infusions of bone marrow cells (BMC): Two of 3 RCT’s found that intracoronary BMC (into the infarct-related artery) improved the function of injured myocardium after acute myocardial infarction or stable 3mo post AMI’s (NEJM 2006;355:1199-1232)…. Left ventricular ejection fraction (LVEF) increased significantly more in the BMC group (mean, 5.5% vs. 3.0%).
Gene Therapy based angiogenesis: direct cardiac injection of fibroblast growth factor and vascular endothelial growth factor to cause angiogenesis.
Hydrotherapy: common in Europe. Alternating warm water (max 40C) baths to arms and foot x15min with a 5 minute cold-water “pouring” at temp <18C. May improve maximal exercise capacity (Eur J Heart Fail 2003;5:527-35).
Infusion System (Benephit Delta): FDA approved in 3/05 to provide targeted renal therapy for pt’s with kidney dysfunction due to CHF (cardiorenal syndrome) and other conditions. A bifurcated infusion catheter allows direct infusion of therapeutic agents into both renal arteries simultaneously, under the premise that targeted delivery will maximize therapeutic benefits while minimizing adverse effects. May decrease the risk of acute kidney failure due to radiocontrast nephropathy in pt’s undergoing minimally invasive cardiovascular procedures and diagnostic tests.
Hypertonic saline: may paradoxically help treat the sodium-retaining state found in pt’s with refractory CHF (J Am Coll Cardiol 2005;45:1997-2007)….every sodium molecule link about three molecules of H2O. A 30-minute infusion of furosemide (500 to 1,000 mg) plus hypertonic saline solution (150 mL of 1.4% to 4.6% sodium chloride) BID for four to six days. Editorial caution that at present, there are not enough data to routinely administer hypertonic saline to heart failure pt’s or liberalize oral sodium intake.
Chronicle Monitor: by Medtronic. An implantable hemodynamic monitoring device that continuously measures intracardiac pressure on an outpatient basis can improve outcomes among NYHA class III/IV pt’s by 33% compared with standard medical care alone (AHA 2005 Scientific Sessions: Abstract 3015, Presented Nov. 14, 2005)…..The monitor continuously tracks intracardiac pressure, body temperature, pt activity, and heart rate, and the measurements are then transmitted from the pt’s home to the clinician’s office via a secure online connection. Less hospitalizations, fewer with worsening heart failure. A manufacturer-sponsored, single-blind trial of the effectiveness of an implantable continuous hemodynamic monitor in reducing heart failure–related clinical events found that it failed to significantly reduce adverse events (COMPASS-HF study. J Am Coll Cardiol 2008;51:1073).
Other: Testosterone (buccally @60 mg/d) increased cardiac output in men with CHF, according to the results of a small placebo-controlled trial, the mechanism appears to involve a reduction in LV afterload (Eur Heart J 2003;24:909-915).
• Functional electrical stimulation (FES) of the legs can enhance the muscle performance and exercise capacity of pt’s with CHF, representing a possible alternative to conventional bicycle training (Eur Heart J 2003;24:871-878). Utrafiltration, the convective removal of iso-osmolar fluid at rates up to 1,500 ml/hr over 12hrs via a central line can improve BNP with minimal change in BP, HR or serum Cr.
• A large, multicenter randomized trial comparing disease-management strategies with conventional follow-up for survivors of a heart-failure (HF) hospitalization failed to show that the intervention reduces mortality or HF rehospitalizations (Arch Intern Med. 2008;168:316-324).
….Intensive disease management called for weekly telephone follow-up and a home visit by a heart-failure nurse during the first month and monthly contact with the nurse thereafter…..multidisciplinary advice given by a physiotherapist, dietician, and social worker were part of the intensive support intervention…..All-cause mortality occurred in 29% of patients in the control group, 27% in the basic support group, and 24% in the intensive support group.
ACEi to highest possible dose or AT 2 (ARB) blocker. Use up to a Cr of 2.6 or K of 5.5. Cardiac rehab (YMCA or PT eval). A randomized trial, high-dose losartan was associated with small but significant improvements in clinical outcomes, compared with a lower dose (Lancet 2009 Nov 17;e-pub ahead of print)…..We are well reminded, however, to uptitrate all medications to the highest efficacious dose (according to the best available trial evidence), as tolerated by the patient. If fails ACEi’s, then use hydralazine or nitrates. See Key Non-Pharmacologic Tx’s |
If Cr >3 mg/dL use Hydralazine-Nitrate Combo: Hydralazine (Apresoline): [25.50,100mg] start @ 25mg TID-QID, incr to max of 150mg QID in 25mg increments qd. Adding isosorbide dinitrate plus hydralazine to standard care for heart failure improves survival for black pt’s (43% reduction in the rate of death)(NEJM 2004;351:2035-2037, 2049-2057, 2112-2114), (lower mortality @ 6% vs. 10% AND lower rate of hospitalization @ for CHF @ 16% vs. 24%), may help create a more favorable balance between nitric oxide and superoxide production.
Isosorbide Dinitrate (Isordil): 10mg TID, increase to max of 80mg TID or 40 QID in 20mg increments qd. If tolerating can switch to Isosorbide Mononitrate (Imdur): 30mg qd, increasing to max of 240mg in qwk increments of 30, 60, 90, 120, 180, 240mg.
BiDil: contain 37.5mg hydralazine + 20mg isosorbide. Start @ 1 tabs TID (max 2 TID), adjust q3-5days. Need an 8-12 hr nitrate-free interval. The first drug approved specifically for African Americans. FDA approved in 6/05. Consider using generic hydralazine and isosorbide dinitrate as costs up to $400/month compared to $60/month for the two generic drugs separately. Isosorbide dinitrate is a vasodilator with effects on both arteries and veins, while Hydralazine is an arterial dilator. Fixed-dose isosorbide dinitrate/hydralazine (ID/H) continues to be safe and effective over the long term in treating African American pt’s with chronic heart failure (Am J Cardiol 2007;100:684-689).
Other: Loop diuretic with thiazides (metolazone sparingly used as booster effect, a K sparing diuretic to conserve K and Mg loss. Add low dose Digoxin if still symptomatic on ACEi (decreases hospitalization, not mortality, NNT is 110, inexpensive), use low dose (0.125mg/d) with goal to improve sx’s. Digoxin therapy appears to reduce mortality in men with heart failure, but only when the serum level is kept between 0.5 and 0.8 ng/mL, according to a report (JAMA 2003;289:871-878). Avoid CCB. Can give sublingual at 2.5mg PRN or prior to exercise to decr dyspnea. Warfarin if Afib, amiodarone the only safe antiarrhythmic. Anticoagulation | Anemia | Testosterone |
Spironolactone (Aldactone): Recommend ed in pt with no significant renal dysfunction or hyperkalemia who are already receiving therapeutic doses of an ACEi and beta-blocker, and have LVEF<40% (advanced, not mild) with symptomatic CHF to decr mortality and hospitalizations by 30%. 25mg/d is the optimal dose (go to 12.5-25mg qod if K rises). Monitor serum K at week 1, 1 month, q3mo x 1yr, then q6mo therafter or 1 week after dose increase. Contra: K >5.5 or Cr >2.5-3.5 mg/dL (CC <30 ml/min) as risk incr K. 10% of males will get gynecomastia. Works well in combo with ACEi, but watch serum K (should be on a loop diuretic), stop if >6. Monitor Cr & K qmo X3, then q3mo X3 the q6mo while on this med. Consider using ½ dose, QOD or even 1x/wk if incr K or Cr. Can be used in all classes of CHF. Rates of hyperkalemia have tripled after since 1999 (RALES trial) when spironolactone prescriptions increased 5-fold (NEJM 2004;351:543-51). An agonist of aldosterone (aldo promotes Mg wasting, arrhythmia and myocardial fibrosis). In CHF the aldo secretion rate is high due to Ang II and serum K as the Ur N/ Ur K ratio is <1 in decompensated CHF (NEJM 2001:245:23). Spironolactone improves left ventricular volumes and function in pt’s with chronic heart failure, it also improved exercise tolerance at 50 mg/day (J Am Coll of Card 2002;40:304-310).
• An aldosterone antagonist (AA)([spironolactone or eplerenone) should be the drug of choice when adding a second renin-angiotensin-aldosterone system (RAAS) blocker to ACEi’s in patients with symptomatic systolic HF despite standard drug therapy, say the researchers behind a 16-trial meta-analysis (Congest Heart Fail 2012; DOI:10.1111/chf.12011)…..The other RAAS blockers included angiotensin receptor blockers (ARBs) and the direct renin inhibitor aliskiren (Tekturna).
• Older age and low EF (<20%) are independent risk factors for azotemia, while NYHA function class and low EF are predictors for hyperkalemia in pt’s taking spironolactone for CHF (BMJ 2003;327:1141-1142).
• In pt’s with mild to moderate chronic systolic CHF, the combination of spironolactone (25mg) and candesartan (8mg) is more effective than candesartan alone in reversing LV hypertrophy and improving LV function (J Am Coll Cardiol 2007;50:591-596,597-599)….after 1 yr was associated with improvements in LV ejection fraction compared with monotherapy (35% versus 26%).
• Spironolactone (mean dose 25 mg/day) may offer protection against the total number of incident fractures in men with CHF a case-control study with 4,735 men suggest (OR = 0.381)(J Am Coll Cardiol 2008;52:135-138).
Eplerenone (Inspra): [25, 50, 100mg tab]: For HTN start at 50mg/d, hold if CC<50 as risk hyperkalemia. May be better tolerated than spironolactone (lower affinity for progesterone & androgen receptors) and can decrease CHF mortality (The Med Let 2003;45:1156). Metabolized by CYP3A4, T- ½ is 4-6hr. Compared to the CCB amlodipine, eplerenone appears to be better tolerated and comparable in reducing SBP (Arch Intern Med 2003;163:1543-1548). Eplerenone has been shown to reduce all-cause mortality following AMI with LV dysfunction (NNT, 43 for 16 mo’s) (NEJM 2003;348:1309-21).
Beta Blockers in CHF: Best when CHF is reasonably compensated (no pulmonary edema or fluid overload) and NYHA class 1-4. Despite concerns about side effects of beta-blockers, these drugs are generally well tolerated by pt’s with heart failure if start low and go slow (Arch Intern Med 2004;164:1370-1371,1389-1394).
• In a meta-analysis of 21 trials, no beta-blocker (atenolol, bisoprolol, bucindolol, carvedilol, metoprolol, nor nebivolol) was superior to any other in improving symptoms and survival in patients with heart failure with low LVEF (BMJ 2013;346:f55)……After a median follow-up of 12 months, b-blockers significantly lowered mortality compared with placebo or standard treatment (odds ratio, 0.7). The individual beta-blockers that significantly lowered mortality compared with placebo or standard treatment were carvedilol (OR, 0.6), bisoprolol (OR, 0.7), and metoprolol (OR, 0.7). However, when different ß-blockers were compared with each other, no differences in risks for death and cardiovascular-related death, improvements in LVEF, drug discontinuation, or other outcomes were observed. Results suggest that the benefits of b-blockers in patients with heart failure are due to a class effect.
• A meta-analysis of beta-blocker trials found that for every 5-bpm reduction in heart rate with beta blockers, mortality fell 18%….regardless of age, sex, cause, use of digoxin and LVEF. (Ann Intern Med 2009;150:784-794)…..The magnitude of the heart rate reduction is statistically significantly associated with the survival benefit of b-blockers in heart failure, whereas the dose of b-blocker is not.
• Patients with heart failure and atrial fibrillation do not benefit as much from beta-blocker therapy as those with sinus rhythm, according to a meta-analysis (JCHF. 2013;1(1):21-28)…..beta-blockers did not reduce hospitalizations for heart failure among patients with atrial fibrillation, whereas they did among those with sinus rhythm……suggest that treatment for those with heart failure and atrial fibrillation “should be approached differently” from those with sinus rhythm.
• Higher beta-blocker doses lead to better outcomes in heart failure patients (J Am Coll Cardiol 2012:Apr 18;e-pub ahead of print)…..At a mean follow-up of 2.5 years, a piecewise linear relation was seen between b-blocker dose and the combined endpoint of mortality and hospitalization, with an inverse association between b-blocker dose and adverse outcome as daily dosages approached 50 mg (roughly equivalent to 100 mg of long-acting metoprolol daily).
• Even in pt’s with diabetes and heart failure, tx with metoprolol CR/XL safely reduces the risk of hospitalization and mortality (Am Heart J 2005;149:159-167).
• Helps prevent progression in pt’s with LV dysfunction and decr hospitalization rate by 35% in all NYHA classes with either metoprolol, bisoprolol or carvedilol (Europ J Heart Failure. 2003;5:281-9).
• Works by decreasing the sympathetic overdrive. There is no ideal dose, must individualize to pt’s heart rate response and ability to tolerate (J Am Coll Card 2002;40:491-8). Consider even in diabetics as masking hypoglycemia not as clinically relevant. If pt get sx’s of vasodilation first increase diuretic, then decrease vasodilator before decreasing beta. If get sx’s of fluid retention first increase diuretic dose. If get sx’s of bradycardia first check dig level. Incr the dose at 2-3wk intervals as tolerated. All lead to insulin resistance in diabetics (vasoconstrictors) except Carvedilol (vasodilator). Long-term beta-blocker therapy improve hemodynamics, but not exercise capacity of CHF pt’s (Am J Cardiol 2003;91:356-360).
• Metoprolol CR/XL significantly reduces mortality and hospitalizations when used to treat heart failure, regardless of the reduction in heart rate achieved (J Am Coll Cardiol 2005;45:252-259).
• Resting heart rate does not accurately reflect the degree of beta blockade in heart failure patients on chronic beta-blocker therapy (Cardiovasc Ther 2009;27:42-48)……Resting heart rate and beta-blocker dose did not correlate with maximal predicted exercise rate (%MPHR) or the chronotropic responsiveness index (CRI), the authors report……often not up-titrated to recommended doses, in large part, the authors speculate, because of a continuing belief that further up-titration will not be achieved once resting heart rate is in a nontachycardic range.
• Findings from a SENIORS substudy suggest that the benefits of beta blockade extend to patients without LV systolic dysfunction (LVSD) (J Am Coll Cardiol 2009;53:2150)……nebivolol benefits patients across a wide range of LV systolic function……The ongoing Japanese Diastolic Heart Failure study of the effects of carvedilol in 800 patients with preserved LV systolic function should provide more-robust data.
• A meta-analysis suggests that improvements in mortality with beta-blockers are more strongly associated with the heart rate achieved than with dose (Ann Intern Med 2009;150:784)……Relative mortality risk was 18% lower for every 5 beat-per-minute reduction in heart rate…..In contrast, no clear association was found between beta-blocker dose and mortality ……the optimal magnitude of heart rate reduction remains uncertain.
• In the SHIFT tiral, Ivabradine reduced the average heart rate by 11 bpm compared with placebo and gave a 26% risk reduction (Lancet 2010;376:875-885)…..the higher the baseline heart rate, the more heart rate dropped off with ivabradine; it fell by a mean 16 bpm for patients at 80 bpm to <87 bpm at baseline and by a mean 22 bpm for those who had been at >87 bpm……There was evidence in the trial that the benefit in those who took ivabradine was not independent of the drug’s effect on heart rate, “indicating that, indeed, heart-rate [reduction] is the mechanism [of benefit] here: nothing beyond heart rate.”
Contra: NYHA class IV, overt fluid overload, HR <60 (or chronotropic incompetence / 2nd-3rd AV block), SBP <100, asthma, COPD with asthma component (use caution if FEV1 <50%), severe peripheral vascular dz, cardiac amyloidosis, severe depression, orthostatic hypotension, severe diabetic hypoglycemic spells. (JAMA 2002;287:7)
Bisoprolol (Zebeta): 1.25mg qd, titrate to max of 10mg qd.
Metoprolol succinate (Toprol XL): start at 12.5-50mg qd, titrate up to 200mg qd. Metoprolol controlled release/extended release (CR/XL), qd, added to standard therapy appears to improve both diastolic and systolic function in pt’s with CHF and decreased LVEF (Echocardiography 2004;21:215-223). In elderly pt’s with HF, the controlled-release/extended release beta-blocker metoprolol succinate (metoprolol CR/XL) improves survival, reduces hospitalizations due to worsening HF, and is well-tolerated (Eur Heart J 2004;25:1300-1309) (MERIT-HF Trial).
Metoprolol tartrate (Lopressor): [50mg] start at 6.25-12.5 mg qd-BID, titrate q2 wk to max of 50-100mg BID.
Coreg (Carvedilol): [3.125, 6.25, 12.5, 25mg] For NYHA Class 2-4. Dose: 3.125mg PO BID X 2wk with food (regardless of age or wt), (observe 1hr after initiate or change the dose), then 6.25 BID X2wk to max dose 25mg BID < 85kg (187#)….May use 50 mg BID for patients over 85 kg. Reduce dose if HR <55.
Coreg CR: [10,20,40 and 80 mg]. Taken in the morning, with food. 10mg = 3.25mg BID. 20 mg/day = Coreg 6.25 mg BID. 40mg qd = 12.5 mg BID. Do crush or chew the caps, but can open them and sprinkle the beads on applesauce. Alcohol can cause faster drug release. Micropump technology which controls the delivery to maintain appropriate amounts of medicine in the body over a 24-hour span. A nonselective beta-blocker, antioxidant, alpha-1 blocker –> decr vascular resistance and sympathetic overdrive of CHF. Has no intrinsic sympathomimetic activity (ISA). At high doses has Ca channel blocking. May initially decompensated a bit, so incr diuretic, take with food and >2hr apart from vasodilating drugs. May not be better than Metoprolol and a lot more expensive. Can safely be started in clinically euvolemic pt’s with severe, chronic CHF (JAMA 2003;289:712-718).
Indications: HTN, postinfarction LV dysfunction, or mild to severe heart failure on ACE or Dig. Good choice in diabetic as alpha-blocking improves insulin sensitivity, hyperglycemia and lipid profile. Higher pharmacy costs, but lower total tx costs (Ann Pharm 2002;36:386). New onset diabetes in 1,151 pt’s with chronic CHF is more likely to develop with metoprolol than with carvedilol after 5 years (Heart 2007;93:968-973)(12.6% vs 10.3%).
If converting pt’s to Carvedilol: If on Metoprolol 50 mg per day or Atenolol 50 mg per day, start @ 6.25 mg BID and titrate dose q1-2wks or start at 3.125mg BID and overlap both for 2wks.
Contra: RAD, 2-3rd deg AVB, severe brady, SSS, brittle DM, allergy, pure diastolic dysfunction, hypotensive, fluid overloaded or hospitalized. Pt’s with CHF combined with asthma tolerate carvedilol poorly, in contrast, pt’s with CHF & COPD tolerate carvedilol well with no significant reversible airflow limitations (J Heart Lung Transplant 2002;21(12):1290-5). SE: Brady–reduce dose and check Dig level (expect 15% incr), pt will feel worse X 8wks with fatigue and light headed (postural), space drug doses 1-2 and/or decr ACE/diuretic.). Avoid NSAID, Ca blockers, ETOH, Tob, Rifampin. Check BP with pt standing. Teach pt about low salt diet, daily wt’s (if >2-3# change notify MD), sx’s of CHF, flexible diuretic regimen. Carvedilol (target dose of 25 mg BID) may have a greater benefit on survival (absolute reduction in mortality of 5.7% over 5 years) than does metoprolol (target dose of 50 mg BID) for the tx of pt’s with CHF who are optimally treated with diuretics and ACEi’s according to findings from the Carvedilol Or Metoprolol European Trial (COMET) (Lancet 2003;362:7-13), some say this study was flawed as they compared Coreg to immediate-release metoprolol not the extended-release form (Toprol XL) that has been shown to improve survival in heart failure, also, the metoprolol doses were probably too low.
• Cardiovascular magnetic resonance (CMR) studies show that carvedilol can reduce the size of the heart and improve its function (reductions in end systolic & diastolic volume index and increased EF by 3% Vs 2% drop) in pt’s with chronic stable CHF (Heart 2004;90:760-764).
• The use of carvedilol in the presence of RAS blockade did not affect glycemic control (Vs 0.15% incr in HbA1c with metoprolol) and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and HTN (isulin sensitivity improved by 9.1% with carvedilol) (JAMA 2004;292:2227-36).
• Tx with carvedilol (Coreg) helps prevent arrhythmias after acute MI, even in pt’s already on ACEi therapy (2.3% Vs 5.4% rate of a-fib / flut) (J Am Coll Cardiol 2005;45:525-530) (CAPRICORN trial).
• In heart failure pt’s, tx with the non-selective beta-blocker carvedilol is associated with improved survival compared to tx with selective beta-blocker metoprolol tartrate, according to a look-back at health insurance claims data on heart failure pt’s treated with the two agents (Int J Cardiol 2005;99:117-124) (carvedilol was independently associated with a 22% reduced risk of death from any cause and a 23% reduced risk of hospitalization from any cause)…..expected costs of inpatient care at 3 years was $10,509 US dollars lower with carvedilol relative to metoprolol.
• Ananalysis of the COMET study shows that carvedilol reduces vascular events to a greater extent than metoprolol (J Am Coll Cardiol 2007; 49:963–971).
Info: Data from 5,791 pt’s reveals that the doses of beta-blockers applied in clinical practice are substantially less that the doses achieved in randomized clinical trials in HF and recommended in national guidelines (Am J Card 2008;102:1524-1529)…..In the first 60 to 90 days after hospital discharge, little up-titration in beta-blocker dosing occurs (only 17.5% and 7.9% of patients were being treated with recommended target doses of carvedilol and metoprolol succinate, respectively)……The total daily target doses recommended in the national guidelines are 50 mg for carvedilol (80 mg for controlled-release carvedilol), 200 mg for metoprolol succinate, and 10 mg for bisoprolol.
Other Beta-blockers: Likely not beneficial: Atenolol (Tenormin): 100mg qd or 50mg BID. Propranolol (Inderal): 60mg TID-QID. Timolol (Blocadren): 20mg BID.
Loop Diuretics: Best considered as “rescue therapy”, not disease modifying like the above. Diuretics reduce the risk of death, delay heart deterioration and improve exercise capacity in pt’s with CHF (Diuretics for heart failure. The Cochrane Database of Systematic Reviews 2006, Issue 1). High-dose loop diuretics (HDLD = 160 mg or more) will worsen survival in chronic heart failure patients with high blood urea nitrogen (BUN) levels, but improve survival for patients with normal BUN levels (1.56 times as likely to die as those on lower doses)(J Am Coll Cardiol 2011;Online Publication, 18 July). See Nephrology chapter for Cardio-renal, Diuretic Resistance & Diuretic Induced ARF |
Torsemide (Demadex): [5,10,20,100mg scored tabs, $20 for #30 tabs of 2-20mg, $76 for 100mg] 10-20mg in 1-2 doses. IV dose = PO dose. With or w/o food. Max of 10mg/d HTN, 40mg/d hepatic dz and 200mg/d for CHF, renal dz. Roche lost it patent in mid-2002 to generic.
• Torasemide (torsemide) compared to furosemide appears to have beneficial effects on cardiac sympathetic nerve activity and left ventricular remodeling in pt’s with CHF via anti-aldosteronergic properties (Heart 2006;92:1434-1440).
• The loop diuretic torasemide (or torsemide 10-20 mg/day) appears to reduce myocardial fibrosis in pt’s with CHF based on endocardial biopsies (J Am Coll Cardiol 2007;50:859-867)….torasemide appears to inhibit the enzyme involved in the myocardial extracellular generation of collagen type 1 molecules, or procollagen type I carboxy-terminal proteinase (PCP).
• A RCT with 237 pt’s with CHF, all on ACEis conlcuded that CHF pt’s treated with torasemide gain a higher benefit in quality of life than furosemide treated pt’s, due to torasemide’s dual effect on both clinical status and social function (Eur J Heart Fail. 2003;5:793-801).
• A RCT of 193 VA pt’s concluded that due to reduced readmission to the hospital (34% vs 58%), the cost of inpatient care for pt’s with CHF is significantly lower with torasemide than with furosemide (Pharmacoeconomics. 2000;17:429-40)….total direct costs were $2124 lower with torasemide than with furosemide (this was prior to when it was even generic).
• Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that pt’s with heart failure who were treated with torsemide and found that compared with furosemide-treated pt’s, torsemide-treated pt’s were less likely to be readmitted for heart failure and for all cardiovascular causes, and were less fatigued (Am J Med. 2001;111:513-20)….If our results are confirmed by blinded trials, torsemide may be the preferred loop diuretic for pt’s with chronic heart failure.
• Torasemide has been shown to be at least as effective as furosemide in terms of total volume of urine excreted and also has a longer duration of action, torasemide is likely to reduce overall tx costs of CHF by reducing hospital admissions and readmissions (Torasemide: a pharmacoeconomic review of its use in chronic heart failure. (Pharmacoeconomics. 2001;19:679-703)….present data support the use of torasemide as a first-line option for diuretic therapy in pt’s with CHF presenting with edema and especially in those pt’s not achieving relief of sx’s with furosemide.
• A Swiss study on 202 ambulatory pt’s concluded that Torasemide with its more complete and less variable bioavailability offers potential clinical and economic advantages over furosemide in the long-term tx in pt’s with CHF (Long-term diuretic tx in heart failure: are there differences between furosemide and torasemide? Schweiz Rundsch Med Prax. 2002;91:1467-75) (lower hospital admission rate of 3.6% Vs furosemide at 5.4%).
• CHF pt’s treated with torasemide gain a higher benefit in quality of life than furosemide treated pt’s, due to torasemide’s dual effect on both clinical status and social function (Eur J Heart Fail. 2003;5:793-801).
• Torasemide is safe and well tolerated in CHF pt’s, data suggests a lower mortality amongst CHF pt’s treated with torasemide (10mg/d)(n=778) compared to furosemide (40mg/d)(n=527)/other diuretics (Torasemide in chronic heart failure: results of the TORIC study. Eur J Heart Fail. 2002;4:507-13)…..a functional improvement and a lower incidence of abnormal serum potassium levels were also observed in pt’s receiving torasemide as compared to those receiving furosemide/other diuretics.
• Bioequivalent doses of torsemide and furosemide found not difference with torsemide with respect to natriuresis or 24-hour ambulatory blood pressure control in subjects with stages 2 and 3 CKD (A double-blind randomized crossover trial of two loop diuretics in chronic kidney disease. Kidney Int. 2003 Aug;64:632-40).
• Torsemide (vs furosamide) is rapidly and fairly completely absorbed independent of the heart failure state (Congest Heart Fail. 2003;9:287-92)…..this pattern of absorption establishes it as the preferred loop diuretic in the otherwise diuretic-resistant heart failure pt.
Furosemide (Lasix): @ 20-80 mg/day, if acute worsening double dose q30-60min until get an effect, or double usual PO dose max 400mg/day Monitor for K and Mg loss. Thiamine supplementation beneficial if taking long-term (Am J Med 1995;98:485).
Bumetanide (Bumex): 0.5-3mg IV/IM or 0.5-5mg PO in 2-3 doses (1mg~ =40mg Lasix). Lasts only 3-4hrs. Max 10mg/d.
Ethacrynic acid (Edecrin): only loop w/o Sulfa, 12.5-100 mg qd. IV start @ 25mg, 1-2mg/hr for CHF, not HTN crisis. Merck stopped production indefinitely in 2003, thus some physicians recommend a graded challenge with Torsemide for CHF pt’s needing a loop, as is contains a sulfa molecule that in non aromatic and unlikely to cross-react with sulfonamide Abx’s (Arch Int Med 2003;163:116). Start Torsemide at 2.5mg PO qdx7d, then incr over 6wks to 10mg/d, then to 40mg (Pt to stop if “any signs of rash, blisters or other adverse events”).
Can add Metolazone (Zaroxolyn): 5-10mg PO 20-30min before IV Lasix (caution if liver dz).
Other: Trimetazidine (20 mg TID) tx in pt’s with diabetes and heart failure can slightly improve systolic myocardial function at rest and during exercise (J Cardiovasc Pharmacol 2004;44:101-8). Trimetazidine is a metabolic agent with anti-ischemic properties operating independently of any hemodynamic changes.
Ex of Furosamide dosing outpatients based on daily wt*:
At target wt: 20mg or 0mg.
2lb (1kg) over: 40mg.
4lb (2kg) over: 80mg.
*Individualize based on pt’s response. A rising need for furosemide is linked with a rising risk for death in elderly heart failure patients (Am Heart J. Published August 2010)….. classified as low dose (up to 59 mg), medium dose (60-119 mg), or high dose (at least 120 mg)……The adjusted mortality hazard ratios with dynamic time-varying furosemide dose were 1.96 with medium-dose furosemide and 3.00 with high-dose furosemide, using low-dose furosemide as the referent……They also observed a “prominent” increase in the risk of renal dysfunction and arrhythmias with furosemide exposure……”Furosemide dose can serve as a powerful, dynamic, and easily used marker of prognosis in heart failure since it likely reflects worsening of heart failure status.”
Due to multiple co-morbidities and multiple mechanisms, treatment will have to tailored as a one-size-fits-all approach is unlikely to be successful. Cardiac rehab (home routine or PT eval). Statins, ACEi’s, and beta blockers are associated with better short- and long-term survival in older patients with heart failure and preserved LV systolic function according to analysis of outcomes of a nationwide sample of 13,533 Medicare recipients (Am J Cardiol 2008;101:217-222). See Key Non-Pharmacologic Tx’s |
Beta-blocker to slow HR to normal levels and decr sympathetics.
CCB’s: mainly non DHP’s such as Verapamil and Diltiazem, can use Norvasc, targeted to control BP and angina.
Diuretics: Aldactone. Give PRN diuretics (furosamide) only (avoid excessive, but some need maintenance diuretics) and regress the LVH. Use of diuretics in obese pt’s with diastolic heart failure appears to reduce sleep-disordered breathing (Chest 2007;132:440-446). Diuretics improve symptoms in patients with diastolic heart failure, and addition of renin-angiotensin system blockade drug (irbesartan or ramipril) can improve left ventricular function according to a study on in 150 patients (Heart 2008;94:573-580).
• A year of aldosterone blockade (spironolactone 25 mg/day or placebo) failed to improve exercise capacity, symptoms, or quality-of-life measures in a placebo-controlled trial of >400 patients with heart failure and LV ejection fractions >50% (JAMA 2013;309:825-826)….However, spironolactone treatment in the study led to significant gains in echocardiographic measures of diastolic function…..the Aldo-DHF trial does little for hopes that aldosterone blockade might turn out to be the long-sought drug therapy with clear hard-end-point benefits in preserved-EF heart failure.
Statins: Cholesterol-lowering statin therapy may improve survival in pt’s with diastolic heart failure (Circulation 2005:July 25) (22% lower risk of death).
Nitrates: to reduce pre-load and for anti-ischemic effects as needed.
ACEIs and ARBs: As opposed to their benefits in systolic heart failure, In a meta-analysis, add-on ACEi’s lowered morbidity and mortality when added to standard therapy for patients with ischemic heart disease and preserved left ventricular function (Ann Intern Med 2009;151:861).
• ACEIs and ARBs may improve symptoms and hospitalization rates but do not appear to reduce mortality in diastolic dysfunction (Lancet 2003;362:777-81 and NEJM 2008;359:2456-67). Like patients with systolic heart failure, diastolic heart failure patients with preserved ejection fraction also appear to benefit from treatment with ACEi’s according to a study on 358 pt’s (Am J Cardiol 2008;101:639-644)(associated with a 30% reduction in the risk of 5-year mortality, HR = 0.73).
• ACEi’s or ARB’s are associated with increased one-year survival in older pt’s with heart failure due to diastolic dysfunction (Am J Cardiol 2003;91:363-365). Lowering blood pressure improves diastolic function irrespective of the type of antihypertensive agent used (The Valsartan in Diastolic Dysfunction = VALIDD study. Lancet 2007;369:2079–2087)…..hypertension needs to be detected early and treated aggressively.
Avoid: Digoxin (unless atrial arrhythmia), positive Inotropes and Afib. Tx with digoxin seems to have little effect on mortality or other outcomes in pt’s with diastolic heart failure pt’s who are in sinus rhythm (Circulation 2006;114:397-403).
Hypertrophic: as above, pacemaker, myectomy.
Restrictive: avoid dig/ Afib.
Diabetics: In obese patients with type 2 diabetes, increased triglyceride stores in the heart can be mobilized by therapeutic prolonged caloric restriction (450 kcal/day; Modifast, Nutrition & Sante for 16 weeks)(J Am Coll Cardiol 2008;52:1006-1012)……”As this mobilization is accompanied by improvements in diastolic function”……”the study implicates the possibility of reversing, at least to some extent, the effects of obesity and diabetes on the heart……At the end of the intervention period, mean body mass index had fallen from 35.6 to 27.5 kg/m, A1c had dropped from 7.9% to 6.3% and myocardial triglyceride content had fallen from 0.88% to 0.64%, in association with improved diastolic function (as reflected by the ratio between the early and atrial filling phase)…..”quantification of myocardial triglyceride stores may in the future be used as a new marker for the risk of heart disease in metabolic disease.” (Approach to pt’s with heart failure and normal ejection fractions. Mayo Clin Proc 2001;76:1047)
Elderly: Conventional heart-failure drugs don’t prolong survival in patients 80 years or older who have HF with preserved ejection fraction, but they do saddle a group already likely to be on multiple medications with additional drug-drug–interaction risk according to researchers based on their five-year observational study (Am J Cardiol 2009;103:829-833)……lack of survival benefit from beta blockers, ACEi’s, ARBs, digoxin and calcium-channel blockers in their analysis is consistent with and complements larger prospective HFPEF trials that found no benefit or only questionable clinical gains from these agents in primarily younger patients……Statins showed a consistent trend toward survival benefit throughout the five years…….survival in patients receiving diuretics appeared to start falling off after about three years…..No medication appeared to reduce the composite of either all-cause hospitalization/mortality or cardiac hospitalization/mortality…..The authors acknowledge that the analysis looked primarily at survival, while symptom status and other quality-of-life issues are also important. “And for many patients, they are more important than anything else.”
Prognosis: Patients with heart failure and preserved ejection fractions are less likely to die of heart failure than of other causes according to a 49 mo study on 881 pt’s (Circulation 2010;121:1393)…..60% of deaths were from cardiovascular causes, including sudden death in 26%, HF in 14%, stroke in 9%, and myocardial infarction in 5%……Cancer was the most common culprit in the 30% of deaths that were noncardiovascular, and 10% of deaths were from unknown causes.
New York Heart Association (NYHA) Classification:
Class 1-4 –> use ACEi, Diuretics, Digoxin. Class 2-3 –> add on as needed Carvedilol, Hydralazine/ Isosorbide Dinitrate (good for dyspnea sx’s). Consider direct vasodilator or alpha blocker in HTN.
“SOMA”:
Class I: asymptomatic. S” with strenuous activity.
Class II: sx’s with moderate activity. Have 16% mortality in 4yr. “O” with ordinary activity.
Class III: sx’s with minimal activity. Have 40% mortality in 4yrs. “M” with minimal activity.
Class IV: sx’s at rest. Have 52% mortality in 1yr. “A” with any activity.
Poor prognostic factors in CHF: diuretic dose (furosemide equivalent) >160 mg per day. Etiology due to ischemic heart dz. Liver function tests abnormal (AST, SGOT >46 U/L, bilirubin >1.2 mg/dL, ALT >46 U/L, alkaline phosphatase >115 U/L, GGT >66 U/L. (Batin P, Wickens M, et al. The importance of abnormalities of liver function tests in predicting mortality in chronic heart failure. Eur Hear J. 1995; 16: 1613-1618). Increasing age, male gender, lower systolic blood pressure on admission, CRP >10 mg/L and creatinine >120 micromol/L are associated with increased mortality risk after hospitalization for acute heart failure (Eur Heart J 2006;27:3011-3017). In patients admitted to the hospital with acute heart failure, abnormal glucose tolerance and diabetes are associated with an increased risk of death in the hospital and in the longer term according to data from 454 consecutive unselected patients admitted to one university hospital for heart failure (Heart 2008;94:296-304). Increased levels of blood urea nitrogen (BUN) are associated with greater long-term mortality in patients with heart failure according to a retrospectively reviewed data on 444 patients (Am J Cardiol 2008;101:1643-1647)…..Patients with a BUN of 17 mg/dL or more had a mortality of 57% snf those with a GFR of 69 or less per mL/min/1.73 per square meter had a 55% mortality rate.
The Seattle Heart Failure Model (SHFM): (http://depts.washington.edu/shfm/). A calculator of projected survival at baseline and after interventions for patients with heart failure. SHFM is designed for use by health care providers knowledgeable in cardiac medicine. In addition to the web-based calculator, there are free, downloadable versions for the Mac OS X, Windows, Palm and PocketPC platforms.
ACC/AHA Stage:
Stages A and B: lacking early signs or sx’s of HF but having increased risk because of specific risk factors or structural cardiac abnormalities.
A: at high risk, but normal heart structure. Stage A pt’s do not demonstrate impairment of left ventricular function (LVF). ACEiI and beta-blockers are often effective in preventing stage A and B HF in pt’s with other risk factors. Calcium-channel antagonists and alpha-blockers are less effective in preventing HF syndrome for pt’s with stage A or B HF. Control of obesity and insulin resistance and management of atherosclerotic disease may reduce progression to HF. A lower systolic BP goal (130 rather than 140 mm Hg) is suggested.
– Treat HTN
– Smoking cessation
– Treat lipid disorders
– Encourage exercise
– Discourage alcohol/illicit drug use
– Control metabolic syndrome
– ACE inhibitors or ARBs
B: pt has structural d/o (LV hypertrophy or fibrosis or prior MI / wall motion abnormalities, valvular disease), but no sx’s. Stage B pt’s are asymptomatic but demonstrate impaired LVF.
– All measures under Stage A
– Beta-blockers
– Devices in selected patients: Implantable defibrillators
C: past or current sx’s with underlying structural dz / LV dysfunction. Usually present with decreased exercise tolerance, fluid retention, or both.
– All measures under Stages A and B
– Dietary salt restriction
– Diuretics for fluid retention
– Drugs in selected patients: Aldosterone antagonist. Digitalis. Hydralazine/nitrates.
– Devices in selected patients: Resynchronization therapy. Implantable defibrillators.
D: end-stage / refractory HF for which specialized advanced tx, such as cardiac transplantation, inotropic support and mechanical circulatory support or compassionate end-of-life care, may be indicated. These pt’s are frequently hospitalized for CHF. Cardiac transplantation is the only established surgical approach to stage D HF but is available to fewer than 2,500 pt’s per year in the U.S.
– Appropriate measures under Stages A, B, and C.
– Decision regarding compassionate end-of-life/hospice care.
– Extraordinary measures: Heart transplant. Chronic inotropes. Permanent mechanical support. Experimental drugs or surgery.
Placement of an ICD: should be considered in those with HF who have nonischemic or ischemic cardiomyopathy and an LVEF </= 30% and are in NYHA class I and have had good functional status for 1 year, and in those with stage C HF as primary and secondary prevention.
(The American Heart Association (AHA) and American College of Cardiology (ACC) 2005 Guidelines for the dx and tx of heart failure. Posted Aug. 16, 2005 at: http://www.americanheart.org and http://www.acc.org)
Other: Cardiac adrenergic nerve activity, evaluated using imaging with iodine-123 metaiodobenzylguanidine (MIBG), is associated with risk of sudden death in pt’s with mild-to-moderate heart failure (Heart 2007;93:1213-1218)….a norepinephrine analog, MIBG can be used to estimate cardiac adrenergic nerve activity. After controlling for age, sex, ethnicity, medical history, use of medications, kidney function, and neurohormonal and echocardiography markers, investigators found an additive effect of AGT and angiotensin II type I receptor (AT1R) genotype risk groups in conferring heightened risk for mortality (OR = 2.2 (ENDO 2007 Annual Meeting: Abstract OR14-3. Presented June 2, 2007).
• LV dyssynchrony is associated with poor clinical outcomes in pt’s with moderate systolic heart failure who undergo successful CABG (J Am Coll Cardiol 2007;50:1315-1323).
• Most chronic heart failure patients think they have years longer to live than they probably do (JAMA 2008;299:2533-2542)…..In a study of 122 ambulatory patients with chronic heart failure, the median patient estimate of time left to live was 13 years, compared with 10 years as predicted by the Seattle Heart Failure Model.
• A study indicate that patients with CHF terminating an exercise test primarily because of dyspnea have an increased incidence of cardiac-related events and poorer cardiopulmonary exercise testing (CPX) markers than those limited by fatigue (general fatigue/leg fatigue) according to a study with 83 pt’s (Am J Card 2008;102:879-882)….Peak oxygen consumption (15.4 vs 17.5 ml o2 · kg-1 · min-1) was significantly lower, whereas minute ventilation/carbon dioxide production slope (38.5 vs 33.9) was significantly higher in the dyspnea subgroup….There were 41 cardiac-related events during the 2-year tracking period. Patients with dyspnea were at significantly higher risk of adverse events (hazard ratio = 2.1).
Link: Ddx | Tx | ICD | See Heart Failure | Orthostatic Hypotension | Vasopressors | TOC |
Step #1: r/o shock, tamponade, valve failure, cardiomyopathy, CHF and MI/ ischemia.
Rate Problem-Too Slow: sinus brady, 2nd degree AVB I and II, pacemaker failure. Too Fast: sinus tach, A-fib/flut, PSVT, VT.
Pump Problem– Primary: MI, cardiomyopathy, myocarditis, ruptured cordae tendineae, acute papillary m. dysfunction, acute AI, prosthetic valve dysfunction, ruptured intraventricular septum. Secondary: drugs, tamponade, PE, atrial myxoma, SVC syndrome.
Volume Problem– Absolute: hemorrhage, GI/renal loss, insensible losses, adrenal insufficiency (aldo). Relative: CNS/spinal lesion, 3rd spacing, tension pneumo, adrenal insufficiency (cortisol), sepsis, drugs that alter vascular tone.
Low DBP: aortic insufficiency, varices (blood bypasses the liver), ACEi’s.
Ddx: Non-neurogenic: Cardiac pump failure, aortic stenosis, bradyarrhythmia, myocardial infarction, myocarditis, pericarditis, tachyarrhythmia, reduced intravascular volume, adrenal insufficiency, burns, dehydration, diabetes insipidus, diarrhea, hemorrhage, salt-losing nephropathy, straining (heavy lifting, urination, or defecation), vomiting, venous pooling, alcohol consumption, fever, heat (e.g., hot environment, hot shower or bath), postprandial dilation of splanchnic vessel beds, prolonged recumbency or standing, sepsis, vigorous exercise with dilation of skeletal vessel beds.
Neurogenic Ddx: Spinal cord problems, syringomyelia, tabes dorsalis, transverse myelitis, tumors, alcoholic polyneuropathy, peripheral nervous system problems, HIV/AIDS, alcoholic polyneuropathy, amyloidosis, diabetes mellitus, dopamine beta-hydroxylase deficiency, Guillain-Barré syndrome, paraneoplastic syndrome, renal failure, B12 or folate deficiency, brain-stem lesions, carotid sinus hypersensitivity, cerebral vascular accidents, dysautonomias, multiple sclerosis, neurocardiogenic syncope, Parkinson’s disease, pure autonomic failure,
Drugs etiologies of Orthostatic hypotension: alpha and beta blockers, antihypertensives, Bromocriptine (Parlodel), diuretics, insulin, MAO inhibitors, marijuana, tranquilizers, narcotics/sedatives, nitrates, phenothiazines, sildenafil (Viagra), sympatholytics, sympathomimetics (with prolonged use), tricyclic antidepressants, vasodilators, vincristine (Oncovin).
Tx: Treat cause. Compression stocking may help. Liberalize sodium and fluid intake if not contraindicated.
Meds that increase BP:
Caffeine: worth a try to see if it reduces hypotension. Suggest 1 or 2 cups of coffee or black tea up to 3 times a day.
Fludrocortisone: A mineralocorticoid start @ 0.1mg PO qd titrate to BID –> incr q weekly. Raises BP by causing sodium and water retention. Be careful using it in patients with heart failure. Monitor serum potassium as can cause hypokalemia.
Midodrine: alpha-1agonist @ 2.5mg/d incr daily to max of 20-30mg/d in TID-QID dose, commonly 10mg BID. Raises blood pressure by causing vasoconstriction and therefore should be avoided in patients with heart disease. Midodrine also decreases heart rate, be careful using it with other meds that lower heart rate such as beta-blockers, digoxin, etc. Tell patients not to be surprised if they get “goose bumps”…midodrine commonly causes hair to stand on end. Caution patients not to take midodrine less than 4 hours before bedtime…to avoid hypertension when lying down.
Prognosis: Nontrauma pt’s who develop transient or episodic hypotension (SBP <100) in the emergency department are at significantly increased risk of dying in the hospital (8% vs 3%) (Chest 2006;130:933,941-946)…. may benefit from a higher level of care such as admission to the ICU. This study of 4790 hospitalized nontrauma pt’s found that 18.5% had hypotension (defined as at least 1 SBP reading <100 mm Hg) while in the ED and that this group had a 3-fold increase in inhospital mortality and a 10-fold increase in sudden unexpected death, compared with pt’s without hypotension. Pt’s with any SBP <80 mm Hg had 6-fold higher mortality and that pt’s with hypotension lasting 1 hour (sustained) had a 3-fold increase in mortality compared with those with only a single hypotension reading (transient). Inhospital mortality rates were 14% in pt’s with sustained hypotension, 8% in those with episodic hypotension.
ICD-9 Codes:
458.0 Orthostatic hypotension
458.1 Chronic hypotension – idiopathic
458.2 Iatrogenic hypotension – postoperative
458.9 Hypotension, unspecified
ICD-10 codes:
(I95.0) Idiopathic hypotension
(I95.1) Orthostatic hypotension
(I95.2) Hypotension due to drugs
(I95.8) Hypotension, other
(I95.9) Hypotension, unspecified
**Ref: (Heart Failure. NEJM 2003;348:2007-18) (Tx of heart failure, Lancet 1998;352:S19) (NEJM 1997;335:490) (Heart failure trial, Lancet 1998;352:S29) (Epidemiology of HF, Lancet 1998;352:S3) (Heart Disease. Pathophysiology of heart failure by Braunwald, 5th ed., 1997, Saunders, pp394-420) (Essential of the dx of heart failure, Am Fam Phys 2000;61:5) (Diagnosis and evaluation of heart failure. Mayo Clin 1997;597-611) (Newer drugs for CHF. Arch IM 1999;159:1177-83) (Spironolactone in CHF. NEJM 1999;341:809-17) (CHF admission guidelines. Ann Emerg Med 1999;34:429-37) (A new model of risk: implications of increasing pulse pressure and systolic blood pressure on cardiovascular disease. J Hypertens 1999;17:S25-8) (Pulse pressure and cardiovascular risk. J Hypertens 1999;17:S21-4) (Measurement of heart rate variability: a clinical tool or a research toy’ J Am Coll Cardiol 1999;34:1878-83) (Bedside Cardiology. By Jules Constant, 1999, Lippincott, pp67-91) (Diastolic Dysfunction. Clev Clin J Med 2000;67:10) (Clinical experience with orthotopic heart transplantation. J Thorac Cardiovasc Surg 1996;112:1496)
HTN Emergency (Malignant HTN):
Links: S/s | Retinopathy | W/u | Captopril Test | Tx | Ddx |
Severe elevations in BP (SBP >220 and/or DBP >120-140) that are complicated by evidence of progressive target organ dysfunction and require immediate BP reduction (not necessarily to normal ranges) to prevent or limit target organ damage. Associated with ongoing (acute & progressive Vs chronic & stable) vascular damage, S/s neurologic/ cardiac/ renal/ retinal/ GI dysfunction present.
Following settings: Aortic Dissection, Acute LV Failure & Pulmonary Edema, ARF or worsening CRF, HTN Encephalopathy, Focal neuro damage indicating a thrombotic/ hemorrhagic stroke, Unstable Angina/ AMI, catecholamine induced HTN (adrenergic crisis from Pheo, cocaine OD, MAOi with tyramine or hyperthyroidism), acute GN, retinopathy. Can also be caused by scleroderma with renal crisis, severe epistaxis, severe body burns, preeclampsia and eclampsia, spinal cord syndromes with autonomic hyperreflexia, rebound HTN (clonidine or beta-blocker), acute head trauma.
S/s: CHF, malaise, weakness, fatigue, N/V, CP, SOB, H-A, somnolence, focal deficits, sz, azotemia, proteinuria, hematuria. Nocturia, dysarthria.
