Uremic cardiomyopathy

Article written and reviewed by Dr Luca Moretti

Uremic cardiomyopathy describes myocardial remodeling that accompanies chronic kidney disease, especially in advanced stages. The picture combines, in varying proportions, left ventricular hypertrophy, interstitial fibrosis, capillary rarefaction and diastolic or systolic dysfunction. It is not synonymous with heart failure in a patient with kidney disease and is not demonstrated by reduced glomerular filtration alone. The CKD-associated cardiomyopathy is instead a phenotypic and causal diagnosis constructed after assessing the numerous concomitant cardiac diseases.

The adjective uremic may suggest a single toxin or a complication confined to dialysis, but both concepts are reductive. Abnormalities of ventricular mass and longitudinal deformation appear even before end-stage kidney disease, while hypertension, anemia, sodium overload, diabetes and mineral disorders act throughout the history of the disease. As kidney function declines, solute retention, inflammation and hemodynamic instability are added. The multifactorial pathogenesis explains why no single correction is sufficient in every patient.

The relationship between kidney and heart is bidirectional. CKD alters myocardial load, metabolism and microcirculation; heart failure, in turn, can reduce renal perfusion and, especially, increase venous pressure, promoting renal congestion and worsening glomerular filtration. A change in creatinine during decongestion or initiation of cardiorenal therapy does not automatically mean tubular injury. Cardiorenal reasoning must distinguish hemodynamic adaptations, true kidney injury and structural progression in both organs.

There are no international criteria assigning a diagnostic score to uremic cardiomyopathy. Assessment integrates the history of CKD, blood pressure and volume over time, electrocardiography, biomarkers, echocardiography and, in selected cases, cardiac magnetic resonance. Coronary artery disease, valvular disease, amyloidosis, genetic cardiomyopathies and endocrine causes should be investigated according to clinical probability. The diagnosis of attribution is more convincing when the phenotype, renal exposure and exclusion of alternatives are all coherent.

Definition, natural history and epidemiology

The classic definition included ventricular hypertrophy, dilation and systolic failure not explained by ischemia, hypertension or valvular disease. In modern practice such a clear separation is rarely possible, because elevated blood pressure, diabetes and coronary artery disease are themselves prevalent components of renal cardiovascular risk. The term remains useful if it indicates a myocardial substrate specifically promoted by the CKD milieu, not if it becomes a catch-all for any heart disease in a patient on dialysis. Nosologic precision prevents omission of treatable diagnoses.

In the historical cohort by Foley and colleagues, approximately three quarters of patients starting kidney replacement therapy had left ventricular hypertrophy on echocardiography. That estimate documents the enormous burden, but cannot be transferred without adjustment to current populations: echocardiographic criteria, age, diabetes, antihypertensive treatment and early access to care have changed. Moreover, mass depends on volume status at the time of the examination. The apparent epidemiology therefore varies with method, selection and phase of the dialysis cycle.

Hypertrophy may be concentric, with thick walls relative to cavity volume, or eccentric, with dilation and increased mass. The former pattern mainly reflects pressure overload and arterial stiffness; the latter is promoted by volume, anemia, an arteriovenous fistula and loss of contractile myocardium. In CKD, geometries often overlap and may change over time. Ventricular geometry provides prognostic information, but does not identify the mechanism by itself.

Typical progression is neither obligatory nor linear. A patient may maintain a normal ejection fraction but develop reduced strain, impaired relaxation and increased filling pressures; another may develop ventricular dilation after ischemia, tachyarrhythmia or repeated intradialytic stunning. Fibrosis and inadequate capillary supply reduce reserve and make the heart vulnerable to acute changes. The subclinical phase therefore represents the most promising time to control blood pressure, volume and kidney disease progression.

Hemodynamic overload and remodeling

Pressure overload results from hypertension, large-artery stiffness, vascular calcification and increased reflected waves. The ventricle generates higher pressure to eject blood into a poorly compliant arterial tree and responds by increasing cardiomyocyte size and wall thickness. Initially this normalizes wall stress, but requires more oxygen and impairs relaxation. Concentric hypertrophy becomes maladaptive when myocyte growth and capillary supply do not proceed together.

Volume overload arises from sodium and water retention, interdialytic gains and, in some patients, arteriovenous access. Preload, atrial size and wall tension increase, while recurrent episodes of pulmonary edema expose the myocardium to marked fluctuations. The weight achieved after dialysis does not automatically represent true euvolemia. Chronic congestion may persist even without obvious edema and sustain both heart failure and resistant hypertension.

Anemia reduces arterial oxygen content and induces increases in cardiac output, heart rate and stroke volume. Over time, this load promotes dilation and hypertrophy, especially when a fistula and hypervolemia coexist. Iron deficiency can also reduce functional capacity independently of hemoglobin level. Correction of anemia must, however, pursue safe clinical targets rather than normalization of blood counts as a presumed direct therapy for fibrosis.

Activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system increases vasoconstriction, sodium retention and profibrotic signaling. Obstructive sleep apnea, pain, anxiety, ischemia and dialysis-related fluctuations can further sustain adrenergic tone. The result is not only increased blood pressure, but greater electrical and metabolic instability. Neurohormonal activation therefore links hemodynamics, remodeling and arrhythmic risk.

Aortic stiffness exposes the ventricle to late afterload and reduces the diastolic pressure available for coronary perfusion. Hypertrophy simultaneously increases the oxygen diffusion distance and compresses small intramural vessels. Even in the absence of epicardial stenosis, coronary reserve can decline and exertion can cause ischemia. Microvascular dysfunction is therefore a structural feature, not simply a synonym for atherosclerosis.

Fibrosis, mineral metabolism and uremic toxins

Histology of CKD-associated cardiomyopathy shows cardiomyocyte hypertrophy, interstitial expansion and fibrosis, with a distribution that does not necessarily match an ischemic scar. Collagen increases stiffness and filling pressure, electrically separates muscle bundles and facilitates heterogeneous conduction. Replacement scarring after myocardial infarction is a different process from diffuse fibrosis. Interstitial fibrosis is the most plausible link between diastolic dysfunction, arrhythmias and reduced reserve.

Fibroblast growth factor 23 rises early in CKD to maintain phosphate excretion. Observational studies have associated high concentrations with greater ventricular mass, while experiments have demonstrated cardiac hypertrophic signaling through FGFR4 independently of the Klotho coreceptor. These findings support biological plausibility but do not prove that lowering FGF23 improves human outcomes. The FGF23-FGFR4 signal is not currently a validated cardiologic target.

Klotho deficiency, hyperphosphatemia, secondary hyperparathyroidism and vitamin D abnormalities are part of CKD-mineral and bone disorder. They promote vascular calcification, stiffness and a proinflammatory milieu, but causal relationships with the myocardium are complex. Phosphate, calcium and PTH should be interpreted serially and together. CKD-MBD is treated according to renal indications, not by pursuing a single FGF23 value or presumed immediate regression of hypertrophy.

Indoxyl sulfate, p-cresyl sulfate and other protein-bound solutes are poorly removed by conventional dialysis and produce profibrotic and oxidative effects in cellular and animal models. Glycation products, carbamylation and microbiome alterations may also contribute to endothelial dysfunction. Clinical associations, however, are not equivalent to therapeutic proof. Uremic toxins constitute a heterogeneous family, and no adsorbent has been shown to cure cardiomyopathy in outcome trials.

Capillary rarefaction makes blood supply inadequate relative to muscle mass and increases susceptibility to ischemia during tachycardia or hypotension. Endothelial dysfunction reduces vasodilation, while calcification and arteriolar remodeling limit reserve. These phenomena can explain pain, persistently elevated troponin and regional abnormalities without a culprit epicardial stenosis. The muscle-capillary mismatch is particularly relevant during rapid ultrafiltration.

Dialysis, myocardial stunning and arteriovenous fistula

Hemodialysis corrects hyperkalemia, acidosis, overload and some uremic solutes, but concentrates into a few hours changes that healthy kidneys distribute throughout the day. Volume removal, temperature, dialysate composition and autonomic response modify blood pressure, perfusion and repolarization. The treatment is lifesaving, but a session can become a repeated hemodynamic stress test. Intradialytic instability should be considered a possible component of the cardiac phenotype.

Studies using echocardiography and perfusion imaging have documented regional reductions in blood flow and contractility during hemodialysis, defined as myocardial stunning when reversible after the session. The phenomenon can occur even without critical epicardial coronary artery disease and is promoted by high ultrafiltration rates and hypotension. Repeated episodes have been associated with subsequent systolic deterioration in cohorts. Myocardial stunning is nevertheless a mechanism, not a diagnosis automatically applicable to every drop in blood pressure.

The long interval in a thrice-weekly regimen promotes greater accumulation of water, potassium and acids, followed by a more demanding session. Arrhythmic and sudden-death risk shows periodicity linked to the dialysis cycle, but also depends on underlying heart disease and the prescription. Dialysate with extreme concentrations can create rapid gradients. Interdialytic dynamics require analysis of weight gain, electrolytes and symptoms across the entire week.

An arteriovenous fistula reduces systemic resistance and increases venous return and cardiac output. Most patients tolerate this adaptation, but a high-flow access can worsen right-sided dilation, pulmonary hypertension or high-output heart failure, especially with anemia and reduced reserve. A flow threshold is not diagnostic in absolute terms. A high-flow fistula becomes clinically significant when access measurements, hemodynamics and symptoms converge.

Examination should look for a bounding pulse, tachycardia, continuous murmur, widened pulse pressure and signs of congestion, but none is specific. Echocardiography, access flow and the ratio of fistula flow to cardiac output help quantify the burden; in complex cases, catheterization with temporary compression may be useful. Flow reduction or ligation requires a strategy for future access. Hemodynamic testing prevents sacrificing a useful fistula for a merely temporal association.

Clinical manifestations and complications

The initial phase is often asymptomatic because hypertrophy maintains the ejection fraction. As relaxation deteriorates, exertional dyspnea, reduced exercise capacity and congestion develop, symptoms that can be mistaken for anemia, deconditioning or simple fluid excess. A response to volume removal does not exclude myocardial disease. Heart failure with preserved ejection fraction is common and requires evidence of elevated filling pressures in the appropriate clinical context.

Systolic dysfunction may result from progression of the substrate, but always mandates an active search for ischemia, silent infarction, tachycardiomyopathy, myocarditis, valvular disease and drug toxicity. A decline in ejection fraction after dialysis may be transient and load-dependent; a persistent reduction between standardized examinations has a different meaning. Persistent ventricular dysfunction should not be attributed to uremia before this assessment.

Syncope and presyncope require urgent assessment of rhythm, blood pressure, ischemia and electrolytes. In patients on dialysis, not all sudden deaths are due to ventricular tachycardia or fibrillation: loop-recorder studies have observed numerous episodes of bradycardia and asystole, especially in relation to the dialysis cycle. This heterogeneity limits strategies based solely on the defibrillator. Sudden cardiac death is a clinical outcome with different mechanisms.

Electrocardiogram and biomarkers

The ECG may show criteria for hypertrophy, axis deviation and secondary repolarization abnormalities, but sensitivity for anatomical mass is limited. Conduction blocks, PR or QRS prolongation, atrial fibrillation and Q waves modify the differential diagnosis. Potassium, calcium, pH and the rate of their changes alter T waves, conduction and QT. ECG interpretation must be linked to the timing of the dialysis session and contemporaneous biochemical values.

Cardiac troponin, especially high-sensitivity troponin, is often chronically elevated in CKD mainly because of structural myocardial injury and microvascular ischemia; reduced clearance may contribute, but does not by itself explain the finding. A value above the 99th percentile demonstrates injury, not necessarily infarction. Diagnosing an acute event requires a serial change and clinical, electrocardiographic or imaging evidence of ischemia. No universal renal threshold replaces the universal definition of myocardial infarction.

BNP and NT-proBNP rise with wall stress and volume, but also with age, atrial fibrillation and reduced kidney function; NT-proBNP is particularly affected by clearance. Very high values retain prognostic significance, whereas the optimal diagnostic threshold varies between nondialysis CKD and dialysis. A trend relative to the patient's usual level can help, provided sampling is standardized. Natriuretic peptides complement examination and imaging; they do not directly measure the amount of fluid.

Complete blood count, ferritin and transferrin saturation define anemia and iron availability; potassium, bicarbonate, calcium, phosphate and PTH identify modifiable factors. Albumin, inflammation and nutritional status help interpret ESA resistance and prognosis without becoming specific myocardial markers. In nondialysis CKD, a combined creatinine-cystatin C estimate may reduce error related to sarcopenia. Integrated biological assessment seeks actionable mechanisms rather than a unique uremic signature.

Echocardiography and myocardial strain

Echocardiography is the initial test because it measures wall thickness, chamber size, ejection fraction, valves and pulmonary pressure. In patients on dialysis, its temporal relationship to the session and volume status should be recorded, because preload and afterload modify dimensions and Doppler indices. Comparing studies performed at different phases can create false progression or regression. Standardization of echocardiography is necessary for any quantitative follow-up.

Ventricular mass is calculated from linear or three-dimensional measurements and indexed to body surface area or height according to laboratory practice and body habitus. Indexing to body surface area may underestimate hypertrophy in obesity, while different formulas are not interchangeable. Relative wall thickness distinguishes concentric remodeling and hypertrophy from eccentric geometry. Indexed ventricular mass should be interpreted with the method and reference values stated.

Diastolic function requires integration of mitral inflow, tissue e', the E/e' ratio, left atrial volume and tricuspid regurgitation velocity, adapting the algorithm to rhythm and valvular disease. No single parameter accurately measures filling pressure in every patient on dialysis. Volume and tachycardia rapidly alter the profile. Diastolic dysfunction is credible when multiple findings agree with symptoms and congestion.

Speckle tracking often detects reduced global longitudinal strain before the ejection fraction falls. GLS reflects the function of subendocardial fibers, which are vulnerable to ischemia and fibrosis, but depends on loading conditions, software, image quality and rhythm. There is no specific cutoff that diagnoses uremic cardiomyopathy. Longitudinal deformation is mainly useful as a sensitive, repeatable measure in the same patient.

New regional abnormalities suggest epicardial ischemia or stunning and require temporal correlation. Echocardiograms during dialysis have shown segments with transiently reduced contraction, but the test is not necessary at every session. When high-output heart failure is suspected, cardiac output, right-sided chambers, pulmonary pressure and response to access compression are assessed. Functional echocardiography thus answers targeted questions beyond the simple measurement of ejection fraction.

Magnetic resonance and tissue characterization

Cardiac magnetic resonance is the reference standard for volumes and mass because of tomographic reconstruction and lower geometric dependence. Well-acquired cine images distinguish hypertrophy, dilation, right ventricular function and regional abnormalities. The advantage is greater when echocardiography has limited windows or discordant measurements. CMR is also affected by hydration status, however, so longitudinal reproducibility requires consistent timing and protocol.

Late gadolinium enhancement identifies focal fibrosis because contrast persists in expanded extracellular spaces. A subendocardial or transmural distribution points toward infarction, whereas a mid-wall or noncoronary pattern suggests a nonischemic process. Diffuse fibrosis may not create sufficient contrast between normal and diseased myocardium and may be missed by LGE. Absence of LGE therefore does not exclude uremic interstitial expansion.

Native T1 mapping measures relaxation time without contrast and is often elevated in advanced kidney failure. It may reflect fibrosis, edema or other compositional changes and varies across scanners, field strengths and sequences. T2 mapping helps identify edema, whereas ECV requires contrast and hematocrit and quantifies extracellular expansion. Elevated native T1 is a sensitive biomarker but not a specific fingerprint of uremic cardiomyopathy.

In patients with acute kidney injury or CKD G4-G5, gadolinium contrast requires explicit assessment of indication and agent. Modern group II agents have a very low risk of nephrogenic systemic fibrosis; the ACR-NKF consensus does not require routine written consent, but recommends that the patient be informed according to local protocol when renal risk is advanced. Dialysis should not be initiated or altered solely to administer a group II agent, while cine imaging and native mapping can already answer many questions. Gadolinium safety should be individualized without denying an essential examination or using contrast that offers no benefit.

Clinical diagnosis and differential diagnosis

The pathway begins by confirming that CKD is chronic and defining its cause, glomerular filtration rate, albuminuria and trajectory. Home or interdialytic blood pressure, weight, residual urine output, between-session gain, anemia, vascular access and dialysis prescription are reconstructed. Symptoms and signs should be linked to rhythm and volume. The cardiorenal timeline helps distinguish progressive remodeling from a recent cardiac event.

A diagnosis of CKD-associated cardiomyopathy is supported by hypertrophy or dysfunction not entirely explained by alternatives, a coherent renal exposure and evidence of diffuse fibrosis or altered longitudinal deformation. It does not require every extrarenal factor to be absent, an unrealistic condition, but does require their contribution to be estimated. A report should name the demonstrated components and degree of attribution. The phenotype-mechanism diagnosis is more useful than a generic label.

Coronary artery disease is common, may be silent in diabetes and should be investigated when symptoms, wall motion, LGE or risk indicate it. Stress imaging, CCTA or coronary angiography is chosen considering calcification, glomerular filtration rate and pretest probability. An epicardial stenosis does not exclude concomitant microvascular dysfunction. Ischemic heart disease should be described separately because it modifies revascularization, antithrombotic therapy and prognosis.

Long-standing hypertension may explain much of the hypertrophy, while aortic stenosis and chronic regurgitation produce characteristic geometries. Mitral and aortic annular calcification is accelerated by CKD-MBD and may become hemodynamically severe. Correction of valvular disease is not replaced by intensifying dialysis. Valvular overload should be quantified according to guidelines and not subsumed into the uremic diagnosis.

Amyloidosis causes increased wall thickness, diastolic dysfunction, strain with relative apical sparing and typical CMR abnormalities, but no single sign is specific in CKD. Evaluation includes serum and urine immunofixation with free light chains interpreted in light of glomerular filtration rate, followed when appropriate by bone scintigraphy or biopsy. ATTR and AL require different pathways. Cardiac amyloidosis is a diagnosis not to be missed because it has its own treatments and prognosis.

Hypertrophic cardiomyopathy, Fabry disease, sarcoidosis and myocarditis enter the differential diagnosis according to morphology, family history and extracardiac features. Fabry disease can cause nephropathy and hypertrophy simultaneously and often shows reduced native T1 before fibrosis, although kidney failure can confound interpretation. LGE patterns and targeted genetic or biochemical tests clarify the suspicion. A shared systemic cause should not be mistaken for a nonspecific consequence of CKD.

Prevention and therapy in nondialysis CKD

There is no drug approved for uremic fibrosis as such. Prevention consists of slowing CKD and reducing the stimuli that generate remodeling, intervening before myocardial mass and interstitium become difficult to reverse. Blood pressure, sodium, volume, diabetes, albuminuria, anemia and atherosclerotic risk require a coordinated plan. Early prevention has stronger evidence than any late attempt to remove established scar.

In adults with hypertension and nondialysis CKD, KDIGO proposes, when tolerated, a systolic blood pressure below 120 mmHg measured with a standardized technique; this value cannot be transferred to casual measurements or to dialysis. Orthostatic hypotension, frailty, coronary artery disease and low diastolic pressure require individualization. Reasonable sodium restriction and diuretics correct volume and enhance blood pressure control. The standardized blood pressure target is a tool, not a goal independent of perfusion.

ACE inhibitors or ARBs are fundamental in albuminuria and are part of therapy for heart failure with reduced ejection fraction when indicated. Creatinine and potassium should be checked after initiation or titration; a limited hemodynamic fall in eGFR does not automatically imply discontinuation. The STOP-ACEi study showed no renal benefit from routine discontinuation in advanced CKD. RAAS inhibition is reduced for symptomatic hypotension, uncontrollable hyperkalemia or other true contraindications.

SGLT2 inhibitors reduce kidney disease progression and heart failure hospitalizations in broad nondialysis populations, with and without diabetes, down to the studied filtration limits. KDIGO 2024 recommends their use in specific profiles with eGFR at least 20 mL/min/1.73 m² and suggests that, once started, they be continued below that threshold unless not tolerated or kidney replacement therapy is initiated. The DAPA-CKD and EMPA-KIDNEY trials did not enroll patients on maintenance dialysis. SGLT2 protection therefore does not justify routine initiation or continuation after dialysis is started.

In heart failure with reduced ejection fraction, an evidence-based beta-blocker, a RAAS inhibitor or sacubitril-valsartan, a mineralocorticoid receptor antagonist and an SGLT2 inhibitor are considered together, adapting doses and monitoring to glomerular filtration rate, potassium and blood pressure. Trials included few patients with very advanced CKD and generally excluded dialysis. Small initial reductions in filtration can be hemodynamic and do not negate benefit. Four-pillar HFrEF therapy requires competent titration, not preemptive avoidance solely because of fear of creatinine elevation.

Steroidal mineralocorticoid receptor antagonists increase hyperkalemia risk when glomerular filtration is low. Finerenone has shown cardiorenal benefits in type 2 diabetes with albuminuric CKD and controlled potassium; FINEARTS-HF also demonstrated a benefit on worsening heart failure events in patients with mildly reduced or preserved ejection fraction, even without diabetes. However, that trial excluded eGFR below 25 mL/min/1.73 m² and dialysis, so it does not demonstrate efficacy in dialysis-associated uremic cardiomyopathy. Potassium binders can facilitate some therapies, without eliminating the need for monitoring. Management of hyperkalemia seeks to preserve effective drugs while keeping safety paramount.

In heart failure with preserved ejection fraction, control of congestion and comorbidities remains central; SGLT2 inhibitors reduce hospitalizations in eligible nondialysis populations. Loop diuretics are useful as long as a renal response remains, whereas in anuria they do not replace ultrafiltration. Excessively rapid weight loss can cause hypoperfusion without resolving interstitial congestion. Effective decongestion is judged by symptoms, signs, blood pressure and trajectory, not by creatinine alone.

Treatment of anemia follows the KDIGO 2026 guideline and begins with evaluation for iron deficiency, bleeding, inflammation and other correctable causes. In patients with G5D, starting an ESA is suggested when hemoglobin is at or below a threshold between 9 and 10 g/dL; in nondialysis CKD the decision is individualized and, for most adults, the threshold lies between 8.5 and 10 g/dL. During maintenance in adults, the hemoglobin target with an ESA should remain below 11.5 g/dL, because higher values increase thrombotic events and stroke without a survival benefit. ESAs at the lowest effective dose reduce transfusions, but are not a cardiac antifibrotic therapy.

Phosphate, calcium and PTH are treated on the basis of serial trends, diet, dialysis, binders, vitamin D or calcimimetics according to CKD stage. Avoiding hypercalcemia and controlling hyperphosphatemia may reduce calcification and stiffness, but no strategy is prescribed solely to lower FGF23 or ventricular wall thickness. Statins and, when indicated, ezetimibe reduce atherosclerotic risk in nondialysis CKD. Control of CKD-MBD and lipids treats defined risks, not an abstract cardiomyopathic signature.

Therapy in dialysis, arrhythmias and transplantation

In a patient on hemodialysis, the first hemodynamic therapy is a prescription that achieves euvolemia without ischemia from rapid fluid removal. Target weight, ultrafiltration rate, session duration, dialysate temperature and sodium are adapted to blood pressure, urine output and interdialytic gain. Bioimpedance and lung ultrasound can complement examination, but no method alone defines dry weight. Tolerable ultrafiltration is often more important than aggressive removal completed at any cost.

Longer or more frequent sessions reduce volume fluctuations and, in the daily FHN trial, improved a composite endpoint that included ventricular mass. The study was small, lasted one year and did not demonstrate a definitive reduction in mortality; it also increased access interventions. The regimen should be selected considering hemodynamic benefit, burden and feasibility. More frequent dialysis is not a universal prescription based on hypertrophy alone.

Recurrent hypotension requires review of weight gain, ultrafiltration rate, medications, temperature, meals and cardiac function. Individualized dialysate cooling can improve stability in some patients, but evidence for major clinical outcomes remains limited. Dialysate potassium, calcium and bicarbonate should avoid excessive gradients without leaving dangerous imbalances. Cardioprotective dialysis prescription is individualized and reassessed after every event.

Evidence for pharmacologic HFrEF therapy in dialysis is much weaker than in nondialysis CKD. A small carvedilol study in dilated cardiomyopathy suggested benefit, but does not establish a class effect or universal dose; dialyzability, bradycardia and hypotension differ among beta-blockers. ACE inhibitors, ARBs, ARNIs and MRAs likewise lack large conclusive trials in this population. HFrEF therapy in dialysis is individualized by the cardiologist and nephrologist, without presenting extrapolations as direct evidence.

The SPin-D study had shown that low-dose spironolactone could be administered with selected monitoring, without a convincing improvement in diastolic function and with more hyperkalemia at higher doses. In 2025, the larger ACHIEVE trial in maintenance dialysis and ALCHEMIST trial in high-risk hemodialysis did not reduce their respective primary composite cardiovascular outcomes. These results do not support spironolactone as routine cardioprotection in dialysis patients, while SGLT2 inhibitors still lack outcome evidence in this population. Digoxin requires extreme caution because of elimination, electrolytes and arrhythmias. The evidence gap has narrowed for mineralocorticoid receptor antagonists, but has not turned into demonstrated benefit.

Atrial fibrillation requires rate or rhythm control adapted to dialyzability and blood pressure. The anticoagulation decision in end-stage kidney disease is complex because both embolic and bleeding risks are high and randomized evidence is limited; warfarin and individual DOACs are not interchangeable. Prior bleeding, vascular access, calciphylaxis, age and preferences modify the balance. Thromboembolic prevention cannot be inferred from the presence of CKD alone.

An ICD is indicated for secondary prevention after cardiac arrest due to VT/VF or sustained ventricular tachycardia with hemodynamic compromise, in the absence of a reversible cause. For primary prevention, cardiomyopathy and ejection-fraction criteria are applied, but in dialysis patients the absolute benefit may be reduced by infections, nonarrhythmic mortality and the frequency of bradyarrhythmias or asystole. The device does not correct potassium abnormalities, hypotension or stunning. Selection for an ICD requires consideration of life expectancy, probable mechanism and procedural risk.

Pacemakers and cardiac resynchronization therapy follow standard electrical and mechanical indications, adapted to infection risk and preservation of venous access. An implantable monitor can clarify infrequent syncope, but is not a routine screening test. Before attributing an event to arrhythmia, hyperkalemia, ischemia, embolism and hypotension are investigated. Device strategy must also preserve the vascular access required for dialysis.

When a fistula contributes to high-output heart failure, banding, revision or ligation can reduce load, but the decision requires reasonable evidence of causality and an access plan. A trial in stable transplant recipients showed reduced ventricular mass after ligation of persistent fistulas, a result that cannot be generalized to every dialysis patient. Preserving a fistula may be valuable if the transplant fails. Access management balances the current heart with future renal needs.

Kidney transplantation corrects many stimuli, improves solute clearance, anemia and freedom from dialysis-related fluctuations, and offers a survival advantage to appropriate candidates. Echocardiographic studies have described reverse remodeling, but CMR analyses and meta-analyses show variable responses rather than universal regression of mass or fibrosis. Blood pressure, rejection, immunosuppression and a persistent fistula continue to have effects. Kidney transplantation is the best physiologic replacement, not a guarantee of cardiac cure.

Follow-up and prognosis

Follow-up is built around risk rather than a schedule identical for everyone. New symptoms, blood pressure changes, arrhythmias, increased volume or transplant candidacy may require earlier echocardiography; a stable patient is monitored according to kidney stage and baseline abnormalities. Using the same modality and dialysis phase increases comparability. Longitudinal surveillance looks for changes capable of modifying therapy, not repetitions without consequences.

Prognosis worsens with marked hypertrophy, dilation, reduced systolic function, elevated filling pressures, fibrosis, abnormal GLS and right ventricular dysfunction. Elevated troponin and natriuretic peptides add information, but do not replace consideration of coronary artery disease, frailty, infections and nutritional status. In dialysis patients, noncardiac risk strongly competes with arrhythmic risk. Multimodal risk stratification is more reliable than any single threshold.

Regression of mass after blood pressure and volume control is favorable, but may partly reflect a smaller cavity or lower hydration at the time of examination. Improvement in ejection fraction does not demonstrate disappearance of fibrosis, and T1 may remain abnormal. Intermediate endpoints should therefore be interpreted together with functional capacity and hospitalizations. Reverse remodeling is desirable, but does not automatically mean normalization of risk.

The KDIGO 2026 document derived from the Controversies Conference on heart and kidney emphasizes integrated care, contextual interpretation of biomarkers and the paucity of data in advanced CKD. It is not a formal guideline dedicated to heart failure, and the first KDIGO guideline specifically addressing HF in CKD is still in development. This methodological distinction avoids turning consensus and incomplete evidence into graded recommendations. Hierarchy of evidence must remain explicit, especially in dialysis.

The best clinical outcome comes from recognizing the phenotype early, treating competing causes and preventing avoidable hemodynamic fluctuations. No uremic label should lead to foregoing evaluation for ischemia, amyloidosis or valvular disease, and no isolated creatinine value should automatically lead to discontinuation of effective therapy. Cardiologist, nephrologist, dialysis team and patient share goals of function, safety and quality of life. Integrated management is the true treatment of a cardiomyopathy arising from multiple interactions.