MELAS Syndrome with Cardiac Involvement: A Multimodality Imaging Approach.

A 49-year-old man presented with chest pain, dyspnea, and lactic acidosis. Left ventricular hypertrophy and myocardial fibrosis were detected. The sequencing of mitochondrial genome (mtDNA) revealed the presence of A to G mtDNA point mutation at position 3243 (m.3243A>G) in tRNALeu(UUR) gene. Diagnosis of cardiac involvement in a patient with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes syndrome (MELAS) was made. Due to increased risk of sudden cardiac death, cardioverter defibrillator was implanted.

Coronary flow reserve is impaired in hypertensive patients with subclinical renal damage.

BACKGROUND: Renal dysfunction is relatively common in patients with primary hypertension (PH). A reduction in coronary vasodilator capacity has recently been reported in patients with renal damage undergoing coronary angiography. We investigated the relationship between coronary flow reserve (CFR) and early renal abnormalities in patients with PH and normal serum creatinine. METHODS: Seventy-six untreated patients were studied. Albuminuria was measured as the albumin-to-creatinine ratio and glomerular filtration rate (eGFR) was estimated by the Cockroft-Gault formula. Chronic kidney disease (CKD) was defined as an eGFR <60 ml/min/1.73 m(2) and/or in the presence of microalbuminuria. Coronary blood flow velocities (cm/s) were measured by Doppler ultrasound at rest and after adenosine administration. CFR was defined as the ratio of hyperemic-to-resting diastolic peak velocities. RESULTS: Prevalence of reduced eGFR, microalbuminuria, CKD, and left ventricular (LV) hypertrophy was 8, 10, 16, and 31%, respectively. Overall, 10% of patients showed impaired CFR (i.e., <2.0). Patients with CKD were more likely to be older (P < 0.05) and of female gender (P < 0.01) and showed higher LV mass index (LVMI) (P < 0.05), lower CFR (P < 0.05; analysis of covariance, P < 0.05), and CFR/LVMI (P < 0.05) than patients with normal renal function. Conversely, patients with impaired CFR showed a significantly higher prevalence of reduced eGFR (chi(2) 5.2, P < 0.05), microalbuminuria (chi(2) 10.2, P < 0.01), and CKD (chi(2) 9.2.1, P < 0.01). Even after adjustment for gender, the presence of CKD entailed a sevenfold higher risk of having impaired CFR (confidence interval 1.17-40.9, P < 0.05). CONCLUSION: Early renal abnormalities are associated with reduced CFR in PH.

Emerging therapeutic strategies in diabetic nephropathy.

Diabetic nephropathy is one of the main causes of end-stage renal disease (ESRD) and is associated with elevated cardiovascular morbidity and mortality. Current renoprotective treatment for diabetic nephropathy includes strict glycemic and optimal blood pressure control, proteinuria/albuminuria reduction and the use of renin-angiotensin-aldosterone system (RAAS) blocking agents. However, the renoprotection provided by these treatments is only partial, and many patients still have progressive disease, thus suggesting that a more effective approach is urgently needed. This review examines emerging strategies for the treatment of diabetic nephropathy, including aggressive RAAS blockade, statins, pentoxifylline, glitazones, ruboxistaurin, as well as sulodexide. Pilot studies that used surrogate end points, mainly albuminuria, will be discussed. New insights suggest that treating microalbuminuric diabetic patients with statins, pentoxifylline, glitazones and sulodexide could be a new approach for reducing the incidence of clinical proteinuria. In diabetic patients with overt nephropathy, the administration of statins, pentoxifylline, sulodexide or aggressive RAAS inhibition, including RAAS dual blockade (i.e., angiotensin-converting enzyme [ACE] inhibitors plus angiotensin receptor blockers or aldosterone antagonists plus ACE inhibitors or angiotensin receptor blockers), seems to be a promising way to preserve renal function and to prevent progression to ESRD. Results of ongoing, long-term trials on major renal and cardiovascular clinical outcomes, as well as on mortality are needed to establish whether the current standard of care of diabetic nephropathy might be improved with these new strategies.

Importance of blood pressure control in chronic kidney disease.

Arterial hypertension together with proteinuria is one of the most important factors associated with the progression of both diabetic and nondiabetic chronic kidney disease. In this review, the role of hypertension and proteinuria in renal disease progression, the BP target that should be achieved to slow the progression of renal damage, and the influence of baseline and current proteinuria on the renoprotective effects of antihypertensive therapy are discussed thoroughly. The interaction between the renoprotective effects of specific antihypertensive agents--mostly angiotensin-converting enzyme inhibitors and angiotensin receptor blockers--and the level of achieved BP also are evaluated. The body of evidence provided by several studies emphasizes the importance of both lowering BP and inhibiting the renin-angiotensin system as specific goals for renal and cardiovascular protection in chronic kidney disease.

Cell transplantation: a novel perspective in the treatment of heart failure.

Stem cell transplantation has been proposed as a novel experimental strategy to treat heart diseases, such as acute myocardial infarction and heart failure. The beneficial effects of transplanted cells may include active contribution to contractile function, passive improvement of cardiac mechanics, induction of neoangiogenesis or other indirect influences on the biology of the heart. Several cell types have been used for cardiac transplantation. These include embryonic stem cells, bone marrow stem cells, and skeletal myoblasts. Encouraging results have been obtained in experimental ischemic and non-ischemic heart disease that show sustained cell survival after transplantation, integration into the host myocardium, and functional improvement of diseased hearts. Furthermore, preliminary data, obtained in patients with acute myocardial infarction, suggest that the observation obtained in the experimental animal may be transferred to the clinical arena in the near future. These observations fueled an exciting period of discovery and high expectations followed by controversies that need to be addressed before this strategy can be added to the therapeutic options for patients with heart disease.

Optimizing therapy in the diabetic patient with renal disease: antihypertensive treatment.

Hypertension, impaired renal function, and proteinuria are commonly associated to the presence of diabetes. They play a major role in the development of cardiovascular and renal damage. Effective antihypertensive treatment reduces the progression of diabetic nephropathy and improves cardiovascular prognosis. Accordingly, tight BP control (<130/80 mmHg) is currently recommended in diabetic patients. Achieving BP targets represents the most important determinant of cardiovascular and renal protection. However, it has been suggested that specific classes of antihypertensive drugs may exert additional organ protection beyond their BP control. The pharmacologic blockade of the renin-angiotensin-aldosterone system has been shown to convey greater renal and cardiovascular protection compared with other classes of drugs. In particular, studies focusing on renal end point suggest that angiotensin-converting enzyme inhibitors (ACEI) are the first-choice drugs in type 1 diabetes. Both ACEI and angiotensin II receptor blockers prevent the progression from microalbuminuria to clinical proteinuria in type 2 diabetes, but angiotensin blockers provide better renoprotection in patients with overt nephropathy. Regarding cardiovascular protection, several studies (but not all) have shown that ACEI exert a protective effect on diabetic patients. Recently, interesting results in favor of angiotensin receptor blockers have been reported in the IDNT, RENAAL, and LIFE studies. It should be noted that to achieve maximal renal and cardiovascular protection, most diabetic patients require integrated therapeutic intervention, including not only several antihypertensive drugs, but statins and antiplatelet therapy as well.

[The role of angiotensin II AT1-receptor antagonists in renal and cardiac protection in type-2 diabetes mellitus]. / Il ruolo degli antagonisti del recettore AT1 dell'angiotensina II nella nefro- e cardioprotezione nel diabete mellito tipo 2.

Blood pressure reduction and intensive antihypertensive treatment are effective in reducing both microvascular and macrovascular complications in type 2 diabetes. Blood pressure target levels < 130/85 or 130/80 mmHg are now recommended. Antagonism of the renin-angiotensin-aldosterone system seems to be an important goal in the treatment of hypertension and diabetes-related complications. The renoprotective role of angiotensin-converting enzyme (ACE)-inhibitors has been well documented in type 1 diabetes; in type 2 diabetes ACE-inhibitors have been deemed more effective than other traditional drugs in reducing the onset of overt nephropathy in microalbuminuric patients (secondary prevention) but not in reducing renal dysfunction in patients with clinical proteinuria (tertiary prevention). Recently, four large trials performed on type 2 diabetes showed that angiotensin II receptor blockers (ARBs) prevent the development of clinical proteinuria in microalbuminuric patients (IRMA and MARVAL studies) and delay the progression of nephropathy towards end-stage renal failure in patients with overt nephropathy (IDNT and RENAAL studies). Moreover, ARBs have been deemed more effective in reducing hospitalizations for heart failure compared to placebo (IDNT and RENAAL studies) and in reducing cardiovascular morbidity and mortality compared to conventional therapy (LIFE study) in type 2 diabetes. In conclusion, ARBs are effective in preventing and delaying renal damage in type 2 diabetes. Thus, the recent guidelines for the prevention and treatment of diabetic nephropathy state that ACE-inhibitors are the first-choice drugs in type 1 diabetes while ARBs are considered as the first-choice drugs in secondary prevention, the same as ACE-inhibitors, and are the unique first-choice drug in tertiary prevention of end-stage renal failure in type 2 diabetes. Finally, ACE-inhibitors and ARBs are both first-choice drugs in cardiovascular prevention in type 2 diabetes.

Renal and cardiovascular protection in type 2 diabetes mellitus: angiotensin II receptor blockers.

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, and target BP less than 130/85 or 130/80 mmHg are now recommended. Inhibition of renin angiotensin aldosterone system (RAAS) plays an essential role in the treatment of hypertension and diabetes-related complications. Studies focusing on renal end-points suggest that angiotensin-converting enzyme inhibitors (ACE-I) are more effective than other traditional agents in reducing the onset of clinical proteinuria in both type 1 and type 2 diabetic patients with incipient nephropathy, mainly in normotensive ones (secondary prevention). However, several small trials in type 2 diabetic patients with overt nephropathy (tertiary prevention) failed to demonstrate a specific renoprotective role for ACE-I, at variance with type 1 diabetes. Three recent large trials address the question of whether angiotensin II receptor blockers (ARB) prevent the development of clinical proteinuria or delay the progression of nephropathy in type 2 diabetes. The IRMA study showed that irbesartan is more effective than conventional therapy in preventing the development of clinical proteinuria and in favoring the regression to normoalbuminuria for comparable BP control in patients with incipient nephropathy. The IDNT and RENAAL trials showed that ARB are more effective than traditional antihypertensive therapies in reducing progression toward end-stage renal failure (ESRF) in type 2 diabetic patients with overt nephropathy independently of changes in BP. Moreover, a reduction in hospitalizations for heart failure was demonstrated for ARB-treated patients compared with placebo. Furthermore, the LIFE study showed that losartan is more effective than conventional therapy in reducing cardiovascular morbidity and mortality in a cohort of diabetic patients with hypertension and left ventricular hypertrophy. In conclusion, ARB seem to be effective in both preventing renal damage and reducing progression toward ESRF in type 2 diabetic patients. Thus, the guidelines for the prevention and treatment of diabetic nephropathy are now changed. In type 1 diabetes ACE-I are the first-choice drug; in type 2 diabetes, ARB are considered first-choice drugs in secondary prevention as well as ACE-I and have been now elected the unique first-choice drug in tertiary prevention of ESRF. Finally, ARB should be considered as the first-choice drug in cardiovascular prevention too, as well as ACE-I.