[Treatment of advanced heart failure with hydralazine and isosorbide dinitrate (author's transl)].
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Adult↗
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The natural history of rheumatic aortic regurgitation and the indications for surgery.
A detailed review was made of 180 patients with severe aortic regurgitation of rheumatic origin. Of these patients, 110 underwent aortic valve replacement. Thirty-nine clinical and haemodynamic factors were studied in an attempt to define those associated with (1) death before surgery, (2) a higher incidence of complications and hospital mortality after surgery, and (3) an unsatisfactory longer-term result of surgery. Only heart failure, radiographic heart size, left ventricular hypertrophy, and ventricular premature beats were associated with death before surgery. No factor predisposed to surgical complications and only preoperative factors associated with an unfavourable result after surgery were advanced heart failure, cardiomyopathy, extreme cardiomegaly, and ventricular premature beats. It is concluded that the indications for operation are: a cardiothoracic ratio of greater than 0-60, or a history of heart failure combined with electrocardiographic evidence of extreme left ventricular hypertrophy. Operation may be safely postponed if these indications are not met, though the presence of ventricular extrasystoles or evidence of independent myocardial disease are further factors which should influence the decision.
Adolescent↗
Comparative whole-exome sequencing of ambulatory patients and transplant recipients with idiopathic dilated cardiomyopathy.
BACKGROUND: Idiopathic dilated cardiomyopathy (DCM) is a major cause of advanced heart failure and heart transplantation (HTx), yet the genetic correlates of progression to HTx and transplant-relevant arrhythmic phenotypes remain incompletely defined. We examined the genetics of idiopathic DCM in a Korean population, focusing on HTx/death and arrhythmic outcomes, to identify adverse outcome-linked genotype-phenotype associations. METHODS: Whole-exome sequencing was performed in 202 Korean patients with idiopathic DCM, including 56 HTx recipients and 146 ambulatory patients, and compared the findings with 1093 population-based controls. Genotype-phenotype correlations were analyzed for major clinical outcomes, including HTx, death, arrhythmias, and left ventricular functional recovery. RESULTS: Pathogenic/likely pathogenic variants were identified in 32% of patients (38% in HTx vs 30% in ambulatory patients). TTN was the most frequently affected gene overall (12%), but LMNA variants predominated in HTx recipients (20% vs 4%, p = 0.001). LMNA carriers showed substantially higher odds of HTx/death (OR 14.65, 95% CI 3.32-139.31; FDR p<0.001), and strong association with arrhythmias, including ventricular tachyarrhythmias and atrial fibrillation. Both missense and loss-of-function LMNA variants were associated with adverse outcomes. In contrast, TNNT2 variants were observed exclusively in ambulatory patients and identified a favorable functional-recovery phenotype, with a greater likelihood of LVEF recovery ≥10 percentage points (OR 6.03, 95% CI 1.52-28.71; FDR p = 0.016). CONCLUSIONS: LMNA variants mark a high-risk transplant-trajectory phenotype in Korean idiopathic DCM. Genetic testing may aid early identification and management of candidates for advanced HF therapies, including HTx and durable MCS.
dilated cardiomyopathy↗
Studies on digitalis. XIV. Is there any correlation between hypomagnesemia and digitalis intoxication?
In a prospective study on digitalis intoxication, low serum magnesium was found in 90 patients, while 388 patients had values above 1.5 mEq/l. Hypomagnesemia was more frequent in women than in men, in those with low body weight and in those with advanced heart failure. More patients with hypomagnesemia than those without had nausea, anorexia, fatigue, flickering of vision and atrial tachycardia with block. Patients with hypomagnesemia also had lower serum potassium than normomagnesemic patients. There was, however, no significant difference in the prevalence of digitalis intoxication or in serum digitoxin concentration. Nor was there any correlation between serum digitoxin and serum magnesium levels.
Body Weight↗
Comparative natriuretic and diuretic efficacy of theophylline ethylenediamine and of bendroflumethiazide during long-term treatment with the potent diuretic bumetanide. Permutation trial tests in patients with congestive heart failure.
The additive natriuretic and diuretic effects of theophylline ethylenediamine and of bendroflumethiazide have been compared in permutation trial tests in patients with advanced congestive heart failure receiving long-term treatment with the highly potent diuretic, bumetanide. Statistical analysis of renal water and electrolyte excretion revealed that theophylline ethylenediamine, 400 mg orally, and bendroflumethiazide, 5 mg orally, had very similar effects, both quantitatively and qualitatively. The mechanism of action of the supplementary diuretics is discussed. It is concluded that theophylline ethylenediamine represents a useful alternative to thiazide diuretics when supplementary natriuretic treatment is considered in patients with congestive heart failure during long-term treatment with potent diuretics. The significance of maintaining the potassium balance during such a combined regimen is stressed.
Bendroflumethiazide↗
Angiotensin-Neprilysin Inhibition and Left Ventricular Assist Device Therapy: Primary Results of the ENVAD-HF Trial.
BACKGROUND: The role of heart failure-specific therapies in left ventricular assist device (LVAD) recipients is unclear, and observational data suggest improved outcomes with neurohormonal blockers. OBJECTIVES: ENVAD-HF (Multicenter, Randomized, Open-Label, Parallel Group, Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients) sought to evaluate the safety and tolerability of the angiotensin-neprilysin inhibitor sacubitril/valsartan vs standard of care (SOC) for managing blood pressure (BP) in HeartMate 3 LVAD recipients. METHODS: ENVAD-HF was a prospective multicenter, randomized, open-label study of sacubitril/valsartan vs SOC for managing BP (mean arterial pressure goal: 75-90 mm Hg) in stable LVAD recipients with 12-month follow-up. The composite primary endpoint was time to death, deterioration in renal function, hyperkalemia, or symptomatic hypotension leading to drug withdrawal. Exploratory endpoints included clinical and biomarker assessments and patient-reported outcomes. RESULTS: In 60 randomized patients (30 in each arm), sacubitril/valsartan compared with SOC demonstrated an HR of 0.42 (95% CI: 0.08-2.18; P = 0.30) for the primary endpoint at 12 months. Two primary endpoints were reached in the sacubitril/valsartan group (1 death and 1 symptomatic hypotension event) compared with 5 in the SOC group (2 deaths, 2 worsening renal function events, and 1 symptomatic hypotension event). Numerical trends in favor of sacubitril/valsartan were noted for other exploratory endpoints, including a reduced number of BP medications (difference: -1.09 [95% CI: -1.52 to -0.66]; P < 0.0001) and a significantly better Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (improvement: +10.6 [95% CI: 2.6-18.7]; P = 0.011). CONCLUSIONS: ENVAD-HF, a prospective randomized controlled trial of angiotensin-neprilysin inhibition in stable HeartMate 3 LVAD recipients, demonstrated the safety and tolerability of this therapy in this unique population. The trial forms the basis for a pivotal trial to investigate the usefulness of HF-specific therapies in the LVAD population. (Sacubitril/Valsartan in Left Ventricular Assist Device Recipients [ENVAD-HF], NCT04103554; A multicENter, randomized, open-label, parallel group, pilot study to evaluate the use of sacubitril/valsartan in HeartMate 3 LVAD recipients, 2019-003888-22).
Humans↗
Extended use of intra-aortic balloon pumping in peripartum cardiomyopathy.
A patient with perinatal cardiomyopathy was greatly benefited physiologically by 7 weeks of intra-aortic balloon pumping. This experience documented that extended pumping can be carried out with only manageable complications. Although the patient survived the hospitalization, she died shortly thereafter of intractable congestive failure. Perinatal cardiomyopathy is a potentially reversible condition. Ventricular assistance by intra-aortic balloon pumping may be sustaining during continued systemic treatment of this entity. Further evaluation for longevity of more advanced congestive heart failure from cardiomyopathies needs further clinical trial.
Adult↗
The natural history of long-term cardiac pacing.
During the past ten years, 504 patients have received one or more pacemakers for complete heart block or other arrhythmia. Of these patients, 306 (61%) are alive. Actuarial analysis shows a steady attrition of 9.4% per year for the first five years, decreasing to 7% per year for the second five years. The overall survival was decreased for patients with congestive heart failure and advanced age and was not affected by the history of Stokes-Adams attacks, initial pulse rate below 50 per minute, or a QRS duration greater than 0.12 second prior to pacing. Cardiac problems were the primary cause of death in 71% of the patients. The natural history of patients with permanent pacemakers depends, more than any other factor, on the function of the left ventricle.
Adult↗
Vasodilator therapy for chronic left ventricular failure.
The effects of chronic oral vasodilator therapy were studied in a group of patients with refractory congestive heart failure. Fifteen patients were treated acutely with intravenous sodium nitroprusside and sublingual isosorbide dinitrate. After continuous therapy with nitroprusside and isosorbide dinitrate for up to 72 hours the patients were then placed on isosorbide dinitrate and oral phenoxybenzamine. Hemodynamic responses to nitroprusside, isosorbide dinitrate, and phenoxybenzamine with isosorbide dinitrate were determined. After a mean follow-up of seven months, nine patients who were receiving isosorbide dinitrate and phenoxybenzamine underwent repeat hemodynamic studies. Beneficial effects of acute vasodilator therapy included a significant reduction in pulmonary capillary wedge pressure and systemic vascular resistance, and significant increases in cardiac index and stroke work index. Mean arterial blood pressure and heart rate were unchanged. During the period of chronic vasodilator administration, no other change in basic therapy with isosorbide dinitrate and phenoxybenzamine (3-21 months), the favorable effects observed acutely were maintained. All patients demonstrated symptomatic improvement with minimal side effects. The beneficial hemodynamic responses that are noted with acute vasodilator therapy in patients in advanced congestive heart failure are maintained with oral therapy on a chronic basis.
Adult↗
[Recent advances in the treatment of heart failure (author's transl)].
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Drug Therapy, Combination↗
Vasodilators: an advance in management of congestive heart failure.
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Heart Failure↗
Bioepidemiology of cardiac amyloidosis.
BACKGROUND: Cardiac amyloidosis, primarily due to immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid, is an increasingly recognized cause of heart failure. Modern diagnostic advances suggest that ATTR, particularly in older adults, may be more prevalent than historically reported. METHODS: All Olmsted County decedents aged ≥40 years from 1970 to 1976 were identified. Available ventricular myocardium from retained paraffin blocks was screened histologically for amyloid using sulfated Alcian blue staining; positive cases underwent grading and proteomic typing by laser microdissection coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Beyond prevalence estimation, this analysis characterizes amyloid type, deposition grade and distribution, associated comorbidities, and cause-of-death patterns, comparing amyloid-positive decedents with age- and sex-matched controls. RESULTS: Of 2,566 eligible deaths, 1,028 autopsy cases with evaluable myocardium formed the study cohort (mean age 70.5 years; 61.1% male; 97% White). Cardiac amyloid was present in 52 cases giving an overall prevalence of 5.1% (95% CI: 3.8-6.6, which rose from 0% under age 60 to 37.5% (95% CI: 21.1-56.3) in those ≥90 years (p < 0.001). While prevalence estimates were higher in men above age 80 compared to women, there was no evidence of an interaction of age and sex (p = 0.90). The quantity of amyloid was sufficient for typing in 38 cases: ATTR (84.2%), AL (7.9%), serum amyloid A (5.3%), and apolipoprotein A-IV (2.6%). Adjusted estimates assuming untyped mild cases were ATTR-type increased ATTR prevalence to 4.5% (95% CI: 3.3-5.9) overall. Comorbidity profiles were similar between amyloid-positive and negative groups, though syncope and leg weakness were more common in amyloid-positive decedents. CONCLUSIONS: In an unselected autopsy cohort, cardiac amyloid was common, particularly ATTR in older adults. Prevalence increased steeply after age 80. These findings suggest that ATTR amyloidosis is not rare and is likely underdiagnosed and has similar prevalence in women and men, despite the male predominance reported in the literature.
Humans↗
Practical management of chronic renal failure.
Initial evaluation of patients with chronic renal failure demands a careful search to exclude reversible causes such as dehydration, obstruction and nephrotoxins. Subsequently, strict management of sodium and fluid intake is necessary to avoid either dehydration or congestive heart failure. As renal failure advances, restriction of dietary protein and potassium and binding of phosphate are indicated. Referral to an end-stage renal disease center should be accomplished early, before and appearance of uremic symptoms, to facilitate a smooth transfer to the next phase of rehabilitative therapy.
Anemia↗
[An indication for a permanent pacemaker : digitialis therapy for cardiac failure with disturbed atrioventricular conduction (author's transl)].
In twenty patients with advanced heart disease with severe cardiac failure and the presence of conduction disturbances before digitalis therapy, but in whom such disturbances were worsened or revealed by the treatment, it was necessary to insert a permanent pacemaker in order to make effective long term digitalisation possible without the risk of excessive bradycardia or pauses due to worsening of atrioventricular block. Six patients died within a period of 9 days to 34 months after insertion of the pacemaker, two were lost from sight, and the other 12 were followed-up regularly for an average period of 20 months, their condition remaining stationary and, in general, satisfactory.
Aged↗
Risk factors for doxorubicin-induced congestive heart failure.
Potential risk factors responsible for development of doxorubicin-induced congestive heart failure were examined through retrospective analysis of 4018 patient records. The overall incidence of drug-induced congestive heart failure was 2.2% (88 cases). The probability of incurring doxorubicin-induced congestive heart failure was related to the total dose of doxorubicin administered. There was a continuum of increasing risk as the cumulative amount of administered drug increased. A weekly dose schedule of doxorubicin was associated with a significantly lower incidence of congestive heart failure than was the usually employed every 3-week schedule. An increase in drug-related congestive heart failure was also seen with advancing patient age. Performance status, sex, race, and tumor type were not risk factors. These data will enable clinicians to better estimate the risk/benefit ratio in individual patients receiving prolonged administration of doxorubicin. They also provide a basis for the investigation of less cardiotoxic anthracycline analogues or for designing measures to prevent doxorubicin-induced cardiomyopathy.
Adolescent↗
Afterload reduction in the treatment of cardiac failure.
The vasodilators produce disparate modifications of cardiac function depending on the differing alterations of preload versus impedance: nitrates principally cause venodilation; nitroprusside, phentolamine and prazosin produce balanced arterial and venous dilation; while hydralazine predominantly effects arterial dilation. Combined nitroprusside and dopamine or dobutamine synergistically enhance low cardiac output and decrease raised left ventricular end-diastolic pressure. Ambulatory oral vasodilator therapy is provided by long-acting nitrates, hydralazine and prazosin alone, combined nitrate-hydralazine and combined prazosin-hydralazine. It is truly remarkable how quickly systemic vasodilators have become established as an important new medical advance in acute and chronic congestive heart failure treatment. In the future, as more experience is gained with the vasodilators and as newer such agents become available, the systemic vasodilators likely will be utilized as often as digitalis in the standard treatment of congestive heart failure.
Blood Pressure↗
Medical complications of obesity.
Obesity leads to several complications that affect many body systems. This paper focuses mainly on the cardiovascular complications, which include coronary heart disease, cerebrovascular disease and stroke, and congestive heart failure; the last may be secondary not only to advanced coronary atherosclerosis, but also to other pathogenetic factors. The increased frequency of coronary heart disease in the obese is largely attributable to the commonly associated hypertension, diabetes mellitus and lipoprotein abnormalities, rather than the adiposity. The lipoprotein disorders that have a role in atherogenesis are decreased plasma concentrations of high-density lipoproteins and elevated plasma concentrations of low-density lipoproteins. Abnormalities in cholesterol metabolism are responsible for the increased frequency of cholelithiasis in obese persons. The factors that mediate the development of cardiovascular and gallbladder complications are correctable by an appropriate program of meal planning and physical activity.
Adult↗
Temporary mechanical support of left ventricular failure following open heart surgery.
Patients coming to open heart surgery with advanced cardiac dysfunction may require mechanical cardiac support to avoid life-threatening low cardiac output in the postoperative period. 15 patients who could not be withdrawn from cardiopulmonary bypass because of low cardiac output were supported with a left heart bypass system (left atrium to ascending aorta). Ten were ultimately separated from the device, 6 were dismissed from the hospital and 4 remain well (the longest 2.6 years postoperative). A major asset of the device is that thoracic reentry is not required when support is discontinued.
Assisted Circulation↗